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Background: Dendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta-analysis examined DC vaccine efficacy and safety for gliomas., Methods: This systematic review and meta-analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated., Results: A total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6-month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%-100%]. Respectively, 12-month OS reported 75% [95%CI: 65%-85%] but declined to 32% [95%CI: 20%-43%] for 24-month OS. 6- and 12-month progression-free survival reached 49% [95%CI: 21%-77%] and 19% [95%CI:8%-30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%-42%], and 26% [95%CI: 10%-42%], though stable disease reached 33% [95%CI: 15%-51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%-57%]., Conclusions: In gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration., (© 2024 John Wiley & Sons Australia, Ltd.)

Currently, conventional immunotherapies for the treatment of non-small cell lung cancer (NSCLC) have low response rates and benefit only a minority of patients, particularly those with advanced disease, so novel therapeutic strategies are urgent deeded. Therapeutic cancer vaccines, a form of active immunotherapy, harness potential to activate the adaptive immune system against tumor cells via antigen cross-presentation. Cancer vaccines can establish enduring immune memory and guard against recurrences. Vaccine-induced tumor cell death prompts antigen epitope spreading, activating functional T cells and thereby sustaining a cancer-immunity cycle. The success of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rendered cancer vaccines a promising avenue, especially when combined with immunotherapy or chemoradiotherapy for NSCLC. This review delves into the intricate antitumor immune mechanisms underlying therapeutic cancer vaccines, enumerates the tumor antigen spectrum of NSCLC, discusses different cancer vaccines progress and summarizes relevant clinical trials. Additionally, we analyze the combination strategies, current limitations, and future prospects of cancer vaccines in NSCLC treatment, aiming to offer fresh insights for their clinical application in managing NSCLC. Overall, cancer vaccines offer promising potential for NSCLC treatment, particularly combining with chemoradiotherapy or immunotherapy could further improve survival in advanced patients. Exploring inhaled vaccines or prophylactic vaccines represents a crucial research avenue., (© 2024 UICC.)

Cell-based therapies hold great potential for cancer immunotherapy. This approach is based on manipulation of dendritic cells to activate immune system against specific cancer antigens. For the development of an effective cell vaccine platform, gene transfer, and cell fusion have been used for modification of dendritic or tumor cells to express immune (co)stimulatory signals and to load dendritic cells with tumor antigens. Both, gene transfer and cell fusion can be achieved by single technique, a cell membrane electroporation. The cell membrane exposed to external electric field becomes temporarily permeable, enabling introduction of genetic material, and also fusogenic, enabling the fusion of cells in the close contact. We tested the feasability of combining gene electrotransfer and electrofusion into a single-step technique and evaluated the effects of electroporation buffer, pulse parameters, and cell membrane fluidity for single or combined method of gene delivery or cell fusdion. We determined the percentage of fused cells expressing green fluorescence protein (GFP) in a murine cell model of melanoma B16F1, cell line used in our previous studies. Our results suggest that gene electrotransfer and cell electrofusion can be applied in a single step. The percentage of viable hybrid cells expressing GFP depends on electric pulse parameters and the composition of the electroporation buffer. Furthermore, our results suggest that cell membrane fluidity is not related to the efficiency of the gene electrotransfer and electrofusion. The protocol is compatible with microfluidic devices, however further optimization of electric pulse parameters and buffers is still needed., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8 + T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment., Competing Interests: Declaration of Competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Personalized neoantigen therapy has shown long-term and stable efficacy in specific patient populations. However, not all patients have sufficient levels of neoantigens for treatment. Although somatic mutations are commonly found in tumours, a significant portion of these mutations do not trigger an immune response. Patients with low mutation burdens continue to exhibit unresponsiveness to this treatment. We propose a design paradigm for neoantigen vaccines by utilizing the highly immunogenic unnatural amino acid p-nitrophenylalanine (pNO 2 Phe) for sequence alteration of somatic mutations that failed to generate neoepitopes. This enhances the immunogenicity of the mutations and transforms it into a suitable candidate for immunotherapy. The nitrated altered epitope vaccines designed according to this paradigm is capable of activating circulating CD8 + T cells and inducing immune cross-reactivity against autologous mutated epitopes in different MHC backgrounds (H-2K b , H-2K d , and human HLA-A02:01), leading to the elimination of tumour cells carrying the mutation. After immunization with the altered epitopes, tumour growth was significantly inhibited. It is noteworthy that nitrated epitopes induce tumour-infiltrating macrophages to differentiate into the M1 phenotype, surprisingly enhancing the MHC II molecule presenting pathway of macrophages. Nitrated epitope-treated macrophages have the potential to cross-activate CD4 + and CD8 + T cells, which may explain why pNO 2 Phe can enhance the immunogenicity of epitopes. Meanwhile, the immunosuppressive microenvironment of the tumour is altered due to the activation of macrophages. The nitrated neoantigen vaccine strategy enables the design of vaccines targeting non-immunogenic tumour mutations, expanding the pool of potential peptides for personalized and shared novel antigen therapy. This approach provides treatment opportunities for patients previously ineligible for new antigen vaccine therapy., (© 2024 John Wiley & Sons Ltd.)

We have previously demonstrated that messenger RNA (mRNA) lipoplexes composed of N -hexadecyl- N , N -dimethylhexadecan-1-aminium bromide (DC-1-16), 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE), and polyethylene glycol-cholesteryl ether (PEG-Chol) exhibited high protein expression in the lungs and spleen of mice after intravenous injection and induced high levels of antigen-specific IgG1 upon immunisation. In this study, we optimised PEG modification in mRNA lipoplexes to reduce mRNA accumulation in the lungs and evaluated the suppression of tumour growth in mice bearing mouse lymphoma E.G7-ovalbumin (OVA) tumours by immunising them with an intravenous injection of OVA mRNA lipoplexes. PEGylation of mRNA lipoplexes with 3 mol% PEG-Chol (LP-DC-1-16-3PCL) prevented agglutination of erythrocytes and reduced accumulation in the lungs. Intravenous injection of LP-DC-1-16-3PCL lipoplexes containing OVA mRNA into mice induced high levels of anti-OVA IgG1 (83,000 mU/mL) in serum, and exhibited a high cytotoxic activity (97%) against E.G7-OVA cells by the splenocytes of mice. Furthermore, immunisation with LP-DC-1-16-3PCL lipoplexes containing OVA mRNA suppressed E.G7-OVA tumour growth compared to control mRNA. Based on these results, LP-DC-1-16-3PCL lipoplexes may be an effective mRNA vaccine for inducing antibody- and cytotoxic cell-mediated immune responses to tumours through intravenous injection.

Cancer vaccines aim at generating cytotoxic CD8 + T cells that kill cancer cells and confer durable tumor regression. Hereto, CD8 + peptide epitopes should be presented by antigen presenting cells to CD8 + T cells in lymphoid tissue. Unfortunately, in unformulated soluble form, peptide antigens are poorly taken up by antigen presenting cells and do not efficiently reach lymph nodes. Hence, the lack of efficient delivery remains a major limitation for successful clinical translation of cancer vaccination using peptide antigens. Here we propose a generic peptide nanoformulation strategy by extending the amino acid sequence of the peptide antigen epitope with 10 glutamic acid residues. The resulting overall anionic charge of the peptide allows encapsulation into lipid nanoparticles (peptide-LNP) by electrostatic interaction with an ionizable cationic lipid. We demonstrate that intravenous injection of peptide-LNP efficiently delivers the peptide to immune cells in the spleen. Peptide-LNP that co-encapsulate an imidazoquinoline TLR7/8 agonist (IMDQ) induce robust innate immune activation in a broad range of immune cell subsets in the spleen. Peptide-LNP containing the minimal CD8 + T cell epitope of the HPV type 16 E7 oncoprotein and IMDQ induces high levels of antigen-specific CD8 + T cells in the blood, and can confer protective immunity against E7-expressing tumors in both prophylactic and therapeutic settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bruno De Geest and Yong Chen have patent #WO2022136641A1 licensed to etherna. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F. nucleatum, thereby enhancing cancer treatment. Although adjuvants have been employed to enhance the immune response, the vaccine's effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens. In this study, we developed a minimalistic, biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F. nucleatum membranes. Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant, the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells, maximizing their ability to achieve effective antigen presentation and strong downstream immune progress. Notably, the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects, eliminating F. nucleatum without affecting intratumoral and gut microbiota. It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F. nucleatum-infected colorectal cancer. Overall, this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options and a poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy is to harness the potential of the immune system against tumor cells. Our previous data showed that the BVax (B cell-based vaccine) can induce therapeutic responses in preclinical models of GBM. In this study, we aimed to characterize the antigenic reactivity of BVax-derived Abs and evaluate their therapeutic potential. We performed immunoproteomics and functional assays in murine models and samples from patients with GBM. Our investigations revealed that BVax distributed throughout the GBM tumor microenvironment and then differentiated into Ab-producing plasmablasts. Proteomics analyses indicated that the Abs produced by BVax had unique reactivity, predominantly targeting factors associated with cell motility and the extracellular matrix. Crucially, these Abs inhibited critical processes such as GBM cell migration and invasion. These findings provide valuable insights into the therapeutic potential of BVax-derived Abs for patients with GBM, pointing toward a novel direction for GBM immunotherapy.

Background: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain., Methods: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models., Results: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of Ad-AURKA/CDK7 promoted the induction and maturation of dendritic cell subsets and augmented multifunctional CD8 + T-cell antitumor immunity. Furthermore, the vaccine induced a long-lasting antitumor effect by promoting the generation of memory CD8 + T cells. Tumor recovery on CD8 + T-cell depletion underscored the indispensable role of these cells in the observed therapeutic effects. The potent efficacy of the Ad-AURKA/CDK7 vaccine was consistently demonstrated in lung metastasis, orthotopic, and humanized tumor models by inducing multifunctional CD8 + T-cell antitumor immune responses., Conclusions: Our findings illustrate that the Ad-AURKA/CDK7 vaccine targeting dual kinases AURKA and CDK7 emerges as a promising and effective therapeutic approach for the treatment of solid tumors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

mRNA vaccines have been revolutionizing disease prevention and treatment. However, their further application is hindered by inflammatory side effects, primarily caused by delivery systems such as lipid nanoparticles (LNPs). In response to this issue, we prepared cationic lipids (mLPs) derived from mildronate, a small-molecule drug, and subsequently developed the LNP (mLNP-69) comprising a low dose of mLP. Compared with the LNP (sLNP) based on SM-102, a commercially available ionizable lipid, mLNP-69 ensures effective mRNA delivery while significantly reducing local inflammation. In preclinical prophylactic and therapeutic B16-OVA melanoma models, mLNP-69 demonstrated successful mRNA cancer vaccine delivery in vivo, effectively preventing tumor occurrence or impeding tumor progression. The results suggest that the cationic lipids derived from mildronate, which exhibit efficient delivery capabilities and minimal inflammatory side effects, hold great promise for clinical application.

Personalized cancer vaccines targeting specific neoantigens have been envisioned as one of the most promising approaches in cancer immunotherapy. However, the physicochemical variability of the identified neoantigens limits their efficacy as well as vaccine manufacturing in a uniform format. Herein, we developed a uniform nanovaccine platform based on poly(2-oxazoline)s (POx) to chemically conjugate neoantigen peptides, regardless of their physicochemical properties. This vaccine system could self-assemble into nanoparticles with uniform size (around 50 nm) and improve antigen accumulation as well as infiltration in the lymph node to increase antigen presentation. In vivo vaccination using this system conjugated with three predicted peptide neoantigen peptides from the MC38 tumor cell line induced 100% robust CD8 + T cell responses and superior tumor clearance compared to free peptides. This POx-based vaccine carrier represents a generalizable approach to increase the availability and efficacy of screened neoantigen peptides for a personalized cancer vaccine.

Cancer immunotherapy has gained popularity in recent years in the search for effective treatment modalities for various malignancies, particularly those that are resistant to conventional chemo- and radiation therapy. Cancer vaccines target the cancer-immunity cycle by boosting the patient's own immune system to recognize and kill cancer cells, thus serving as both preventative and curative therapeutic tools. Among the different types of cancer vaccines, those based on nanotechnology have shown great promise in advancing the field of cancer immunotherapy. Lipid-based nanoparticles (NPs) have become the most advanced platforms for cancer vaccine delivery, but polymer-based NPs have also received considerable interest. This Review aims to provide an overview of the nanotechnology-enabled cancer vaccine landscape, focusing on recent advances in lipid- and polymer-based nanovaccines and their hybrid structures and discussing the challenges against the clinical translation of these important nanomedicines.

Messenger RNA (mRNA) vaccines are promising platforms for cancer immunotherapy because of their potential to encode for a variety of tumor antigens, high tolerability, and capacity to induce strong antitumor immune responses. However, the clinical translation of mRNA cancer vaccines can be hindered by the inefficient delivery of mRNA in vivo . In this review, we provide an overview of mRNA cancer vaccines by discussing their utility in treating melanoma. Specifically, we begin our review by describing the barriers that can impede mRNA delivery to target cells. We then review native mRNA structure and discuss various modification methods shown to enhance mRNA stability and transfection. Next, we outline the advantages and challenges of three nonviral carrier platforms (lipid nanoparticles, polymeric nanoparticles, and lipopolyplexes) frequently used for mRNA delivery. Last, we summarize preclinical and clinical studies that have investigated nonviral mRNA vaccines for the treatment of melanoma. In writing this review, we aim to highlight innovative nonviral strategies designed to address mRNA delivery challenges while emphasizing the exciting potential of mRNA vaccines as next-generation therapies for the treatment of cancers.

With the COVID-19 pandemic, the importance of vaccines has been widely recognized and has led to increased research and development efforts. Vaccines also play a crucial role in cancer treatment by activating the immune system to target and destroy cancer cells. However, enhancing the efficacy of cancer vaccines remains a challenge. Adjuvants, which enhance the immune response to antigens and improve vaccine effectiveness, have faced limitations in recent years, resulting in few novel adjuvants being identified. The advancement of artificial intelligence (AI) technology in drug development has provided a foundation for adjuvant screening and application, leading to a diversification of adjuvants. This article reviews the significant role of tumor vaccines in basic research and clinical treatment and explores the use of AI technology to screen novel adjuvants from databases. The findings of this review offer valuable insights for the development of new adjuvants for next-generation vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zheng, Coghi, Chen, Dong and Fan.)

Background: Glioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytes., Methods: This is a single-arm, monocentric, phase II trial in two steps according to Simon's design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test)., Results: By December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery., Conclusions: This combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ridolfi, Gurrieri, Riva, Bulgarelli, De Rosa, Guidoboni, Fausti, Ranallo, Calpona, Tazzari, Petrini, Granato, Pancisi, Foca, Dall'Agata, Bondi, Amadori, Cortesi, Zani, Ancarani, Gamboni, Polselli, Pasini, Bartolini, Maimone, Arpa and Tosatto.)

Abstract: Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that "polyvalent" vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR repertoire from healthy individuals using RNA-seq data. An average of 52 somatic mutations per patient (range, 2-172) were identified, and ≥2 (median, 15) high-quality neoantigens were predicted for 56 of 58 FL samples. The predicted neoantigen peptides were composed of missense mutations (77%), indels (9%), gene fusions (3%), and BCR sequences (11%). Building off of these preclinical analyses, we initiated a pilot clinical trial using personalized neoantigen vaccination combined with PD-1 blockade in patients with relapsed or refractory FL (#NCT03121677). Synthetic long peptide vaccines targeting predicted high-quality neoantigens were successfully synthesized for and administered to all 4 patients enrolled. Initial results demonstrate feasibility, safety, and potential immunologic and clinical responses. Our study suggests that a genomics-driven personalized cancer vaccine strategy is feasible for patients with FL, and this may overcome prior challenges in the field. This trial was registered at www.ClinicalTrials.gov as #NCT03121677., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients., (© 2024. The Author(s).)

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints., (© 2024. The Author(s).)

Personalized T-cell therapy is emerging as a pivotal treatment of cancer care by tailoring cellular therapies to individual genetic and antigenic profiles, echoing the exciting success of personalized vaccines. We describe here the parallel evolution and analogies of cancer vaccines and T-cell therapies., (© 2024 Chiffelle and Harari.)

Homologous animal cell product was obtained in protocol developed for female BALB/c mice. Dendritic cell (DC) migration from the injection site into the draining lymph nodes was evaluated. The number of DC labeled with carboxyfluorescein succinimidyl ester (CFSE) in draining lymph nodes increased from 5.3% (16 h) to 13.3% (48 h) (p=0.028) with a maximum at 72 h (15.4%, p=0.003). The immunophenotype of CFSE-DC detected in murine lymph nodes corresponded to the immunophenotype of mature vaccine DCs: they expressed differentiation markers CD11c, CD80, CD83, and CD86 (p>0.05 vs initial DC)., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

In situ cancer vaccination refers to any approach that exploits tumour antigens available at a tumour site to induce tumour-specific adaptive immune responses. These approaches hold great promise for the treatment of many solid tumours, with numerous candidate drugs under preclinical or clinical evaluation and several products already approved. However, there are challenges in the development of effective in situ cancer vaccines. For example, inadequate release of tumour antigens from tumour cells limits antigen uptake by immune cells; insufficient antigen processing by antigen-presenting cells restricts the generation of antigen-specific T cell responses; and the suppressive immune microenvironment of the tumour leads to exhaustion and death of effector cells. Rationally designed delivery technologies such as lipid nanoparticles, hydrogels, scaffolds and polymeric nanoparticles are uniquely suited to overcome these challenges through the targeted delivery of therapeutics to tumour cells, immune cells or the extracellular matrix. Here, we discuss delivery technologies that have the potential to reduce various clinical barriers for in situ cancer vaccines. We also provide our perspective on this emerging field that lies at the interface of cancer vaccine biology and delivery technologies., (© 2024. Springer Nature Limited.)

The present review focuses on synthetic peptide-based vaccine strategies in the context of anticancer intervention, paying attention to critical aspects such as peptide epitope selection, adjuvant integration, and nuanced classification of synthetic peptide cancer vaccines. Within this discussion, we delve into the diverse array of synthetic peptide-based anticancer vaccines, each derived from tumor-associated antigens (TAAs), including melanoma antigen recognized by T cells 1 (Melan-A or MART-1), mucin 1 (MUC1), human epidermal growth factor receptor 2 (HER-2), tumor protein 53 (p53), human telomerase reverse transcriptase (hTERT), survivin, folate receptor (FR), cancer-testis antigen 1 (NY-ESO-1), and prostate-specific antigen (PSA). We also describe the synthetic peptide-based vaccines developed for cancers triggered by oncovirus, such as human papillomavirus (HPV), and hepatitis C virus (HCV). Additionally, the potential synergy of peptide-based vaccines with common therapeutics in cancer was considered. The last part of our discussion deals with the realm of the peptide-based vaccines delivery, highlighting its role in translating the most promising candidates into effective clinical strategies. Although this discussion does not cover all the ongoing peptide vaccine investigations, it aims at offering valuable insights into the chemical modifications and the structural complexities of anticancer peptide-based vaccines., (© 2024 European Peptide Society and John Wiley & Sons, Ltd.)

mRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with β-glucans (βGlus), a potential adjuvant for vaccines, encapsulated within LNPs (βGlus/mRNA@LNPs). The βGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor-bearing mice, βGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen-specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral βGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle-free and user-friendly administration for widespread adoption and self-administration., (© 2024 Wiley‐VCH GmbH.)

A first-in-human trial demonstrated that a vaccine targeting the histone mutation H3K27M can induce an immune response, in a mutation-specific manner, in patients with diffuse midline glioma. In a recent study by Boschert et al., the same group now dissects the functional immune response triggered after effective vaccination of one of the patients, who has been in remission for over 3 years. The H3K27M peptide vaccine, named H3-vac, induces a CD4 + T-cell-specific immune response in this patient and expands the repertoire of polyclonal H3K27M-specific T-cell receptors. A clonal H3K27M-reactive B-cell population was also detected in the patient's cerebrospinal fluid. Importantly, the immune response is induced across various human leukocyte antigen alleleotypes, indicating the potential efficacy of the vaccine in diverse populations. By exploring in detail the immune response linked to this patient's long-term survival, the authors prove peptide vaccinations as a viable therapeutic approach. This paves the way for personalised therapies harnessing immunogenic T- and B-cell responses against different tumour types., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Therapeutic cancer vaccines have been a subject of research for several decades as potential new weapons to tackle malignancies. Their goal is to induce a long-lasting and efficient antitumour-directed immune response, capable of mediating tumour regression, preventing tumour progression, and eradicating minimal residual disease, while avoiding major adverse effects. Development of new vaccine technologies and antigen prediction methods has led to significant improvements in cancer vaccine efficacy. However, for their successful clinical application, certain obstacles still need to be overcome, especially tumour-mediated immunosuppression and escape mechanisms. In this review, we introduce therapeutic cancer vaccines and subsequently discuss combination approaches of next-generation cancer vaccines and existing immunotherapies, particularly immune checkpoint inhibitors (ICIs) and adoptive cell transfer/cell-based immunotherapies., Competing Interests: Declaration of interests A.H.: consultancy fees and honoraria from Astra-Zeneca, BMS, MSD, BeiGene, Abbvie, Roche, and Incyte. P.B.: consultancy fees from Astra-Zeneca, BMS, MSD, and BeiGene; research funding from BMS; honoraria from Roche, MSD, BMS, and Astra-Zeneca. A.B. declares no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

New adjuvants that trigger cellular immune responses are urgently needed for the effective development of cancer and virus vaccines. Motivated by recent discoveries that show activation of type I interferon (IFN-I) signaling boosts T cell immunity, this study proposes that targeting this pathway can be a strategic approach to identify novel vaccine adjuvants. Consequently, a comprehensive chemical screening of 6,800 small molecules is performed, which results in the discovery of the natural compound picrasidine S (PS) as an IFN-I inducer. Further analysis reveals that PS acts as a powerful adjuvant, significantly enhancing both humoral and cellular immune responses. At the molecular level, PS initiates the activation of the cGAS-IFN-I pathway, leading to an enhanced T cell response. PS vaccination notably increases the population of CD8+ central memory (T CM )-like cells and boosts the CD8+ T cell-mediated anti-tumor immune response. Thus, this study identifies PS as a promising candidate for developing vaccine adjuvants in cancer prevention., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self-tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high-density lipoprotein-mimicking nanodiscs, and developing nano-based artificial antigen-presenting cells such as dendritic cell-derived-exosomes are amongst the new developed technologies to enhance antigen-presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response., (© 2024 Wiley Periodicals LLC.)

Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine. In addition, immunofluorescence data demonstrated that the treated group exhibited significantly more and larger tertiary lymphoid structures (TLSs) than the untreated group. The presence of TLS was associated with enhanced T cell infiltration, and a large number of proliferating T cells were found in the treated group. Furthermore, the flow cytometry results showed that in the treatment group, cytotoxic T lymphocytes exhibited partial polarization toward effector memory T cells and were activated to play a lethal role in the peripheral immunological organs. Furthermore, a substantial proportion of B cells in the draining lymph nodes expressed CD40 and CD86. Surprisingly, quantitative polymerase chain reaction indicated that a high expression of cytokines, including chemokines in brain tumors and immune tissues, induced the differentiation, development, and chemokine migration of immune cells in the treated group. Our study data demonstrate that IE1 or IE1mut vaccination has a favorable effect in glioma mice models. This study holds substantial implications for identifying new and effective therapeutic targets within GBM., (© 2024. The Author(s).)

IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2.0 were observed. Grade 1/2 injection site reactions were observed in five of seven patients. IgG and IgM responses to Emm55 peptides and known melanoma antigens were seen in the peripheral blood, suggesting that IFx-Hu2.0 acts as an individualized "in situ vaccine." Three of four patients previously refractory to anti-PD1 experienced clinical benefit upon subsequent anti-PD1-based treatment. Therefore, this approach is feasible, and clinical/correlative outcomes warrant further investigation for treating patients with metastatic melanoma with an immune priming agent., (©2024 The Authors; Published by the American Association for Cancer Research.)

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronavirus pandemic, the development of mRNA vaccines has seen substantial progress and widespread adoption. In the present review, the development of mRNA vaccines, their mechanisms of action, factors influencing their function and the current clinical applications of the vaccine are discussed. A focus is placed on the application of mRNA vaccines in cancer, with the aim of highlighting unique advances and the remaining challenges of this novel and promising therapeutic approach.

Purpose: Although mRNA vaccines have shown certain clinical benefits in multiple malignancies, their therapeutic efficacies against hepatocellular carcinoma (HCC) remains uncertain. This study focused on establishing a novel risk score system based on immune subtypes so as to identify optimal HCC mRNA vaccination population., Methods: GEPIA, cBioPortal and TIMER databases were utilized to identify candidate genes for mRNA vaccination in HCC. Subsequently, immune subtypes were constructed based on the candidate genes. According to the differential expressed genes among various immune subtypes, a risk score system was established using machine learning algorithm. Besides, multi-color immunofluorescence of tumor tissues from 72 HCC patients were applied to validate the feasibility and efficiency of the risk score system., Results: Twelve overexpressed and mutated genes associated with poor survival and APCs infiltration were identified as potential candidate targets for mRNA vaccination. Three immune subtypes (e.g. IS1, IS2 and IS3) with distinct clinicopathological and molecular profiles were constructed according to the 12 candidate genes. Based on the immune subtype, a risk score system was developed, and according to the risk score from low to high, HCC patients were classified into four subgroups on average (e.g. RS1, RS2, RS3 and RS4). RS4 mainly overlapped with IS3, RS1 with IS2, and RS2+RS3 with IS1. ROC analysis also suggested the significant capacity of the risk score to distinguish between the three immune subtypes. Higher risk score exhibited robustly predictive ability for worse survival, which was further independently proved by multi-color immunofluorescence of HCC samples. Notably, RS4 tumors exhibited an increased immunosuppressive phenotype, higher expression of the twelve potential candidate targets and increased genome altered fraction, and therefore might benefit more from vaccination., Conclusions: This novel risk score system based on immune subtypes enabled the identification of RS4 tumor that, due to its highly immunosuppressive microenvironment, may benefit from HCC mRNA vaccination., (© 2024. Springer Nature Switzerland AG.)

Introduction: Tertiary lymphoid structures (TLS) arise at chronic inflammatory sites where they function as miniature lymph nodes to generate immune responses, which can be beneficial or detrimental, in diseases as diverse as autoimmunity, chronic infections and cancer. A growing number of studies show that a TLS presence in tumors from cancer patients treated with immune checkpoint inhibitors is closely linked with improved clinical outcomes. TLS may foster the generation of specific anti-tumor immune responses and immunological memory that recognizes a patient's own tumor. Due to repeated rounds of chronic inflammation, some tumor-associated TLS may be immunologically inactive, with immune checkpoint inhibitors functioning to revitalize them through pathway activation., Areas Covered: This review summarizes work on TLS and how they mediate immune responses in human tumors. We also explore TLS as potential prognostic and predictive biomarkers for immunotherapy., Expert Opinion: The presence of TLS in human tumors has been linked with a better clinical prognosis, response to treatment(s) and overall survival. TLS provide a structured microenvironment for the activation, expansion and maturation of immune cells at the tumor site. These activities can enhance the efficacy of immunotherapeutic treatments such as checkpoint inhibitors and cancer vaccines by revitalizing local anti-tumor immunity.

Chimeric antigen receptor (CAR-T) cell therapy is a newly developed immunotherapy strategy and has achieved satisfactory outcomes in the treatment of hematological malignancies. However, some adverse effects related to CAR-T cell therapy have to be resolved before it is widely used in clinics as a cancer treatment. Furthermore, the application of CAR-T cell therapy in the treatment of solid tumors has been hampered by numerous limitations. Therefore, it is essential to explore novel strategies to improve the therapeutic effect of CAR-T cell therapy. In this review, we summarized the recently developed strategies aimed at optimizing the generation of CAR-T cells and improving the anti-tumor efficiency of CAR-T cell therapy. Furthermore, the discovery of new targets for CAR-T cell therapy and the combined treatment strategies of CAR-T cell therapy with chemotherapy, radiotherapy, cancer vaccines and nanomaterials are highlighted., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Ferroptosis, a necrotic, iron-dependent controlled cell death mechanism, is distinguished by the development of lipid peroxides to fatal proportions. Malignant tumours, influenced by iron to promote fast development, are vulnerable to ferroptosis. Based upon mounting evidence it has been observed that ferroptosis may be immunogenic and hence may complement immunotherapies. A new approach includes iron oxide-loaded nano-vaccines (IONVs), having supremacy for the traits of the tumour microenvironment (TME) to deliver specific antigens through improving the immunostimulatory capacity by molecular disintegration and reversible covalent bonds that target the tumour cells and induce ferroptosis. Apart from IONVs, another newer approach to induce ferroptosis in tumour cells is through oncolytic virus (OVs). One such oncolytic virus is the Newcastle Disease Virus (NDV), which can only multiply in cancer cells through the p53-SLC7A11-GPX4 pathway that leads to elevated levels of lipid peroxide and intracellular reactive oxygen species leading to the induction of ferroptosis that induce ferritinophagy., (© 2024 John Wiley & Sons Ltd.)

Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell-based vaccination is limited by interference from immunosuppressive senescence-associated secretory phenotype and pro-tumorigenic capacity of senescent cells. Here, a senescent cancer cell-based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane-coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death-induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma-challenged mice with fewer side effects when combined with αPD-1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell-based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells., (© 2024 Wiley Periodicals LLC.)

Cancer stem cells (CSCs) can self-renew and differentiate, contributing to tumor heterogeneity, metastasis, and recurrence. Their resistance to therapies, including immunotherapy, underscores the importance of targeting them for complete remission and relapse prevention. Olfactomedin 4 (OLFM4), a marker associated with various cancers such as colorectal cancer, is expressed on CSCs promoting immune evasion and tumorigenesis. However, its potential as a target for CSC-specific immunotherapy remains underexplored. The primary aim of this study is to evaluate the effectiveness of targeting OLFM4 with dendritic cell (DC)-based vaccines in inhibiting tumor growth and metastasis. To improve antigen delivery and immune response, OLFM4 was conjugated with a protein-transduction domain (PTD) from the antennapedia of Drosophila called penetratin, creating a fusion protein (P-OLFM4). The efficacy of DCs pulsed with P-OLFM4 (DCs [P-OLFM4]) was compared to DCs pulsed with OLFM4 (DCs [OLFM4]) and PBS (DCs [PBS]). DCs [P-OLFM4] inhibited tumor growth by 91.2 % and significantly reduced lung metastasis of OLFM4+ melanoma cells by 97 %, compared to the DCs [PBS]. DCs [OLFM4] also demonstrated a reduction in lung metastasis by 59.7 % compared to DCs [PBS]. Immunization with DCs [P-OLFM4] enhanced OLFM4-specific T-cell proliferation, interferon-γ production, and cytotoxic T cell activity in mice. The results indicate that OLFM4 is a viable target for CSC-focused immunotherapy. DC [P-OLFM4] vaccines can elicit robust immune responses, significantly inhibiting tumor growth and metastasis. This strategy holds promise for developing more effective cancer treatments that specifically target CSCs, potentially leading to better patient outcomes by reducing the likelihood of tumor relapse and metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The corresponding author, Seung-Yong Seong, is a professor at SNU and the CEO of Shaperon Inc. The licensing of the patent for penetratin-OLFM4 from SNU to Shaperon is under consideration but not yet decided., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Multiple myeloma (MM) is a hematological cancer marked by plasma cell accumulation in the bone marrow. Despite treatment advancements, MM remains incurable in most patients. MM-associated immune dysregulation fosters disease progression, prompting research into immunotherapy to combat the disease. An area of immunotherapy investigation is the design of myeloma vaccine therapy to reverse tumor-associated immune suppression and elicit tumor-specific immune responses to effectively target MM cells. This article reviews vaccine immunotherapy for MM, categorizing findings by antigen type and delivery method. Antigens include idiotype (Id), tumor-associated (TAA), tumor-specific (TSA), and whole tumor lysate. Myeloma vaccination has so far shown limited clinical efficacy. However, further studies are essential to optimize various aspects, including antigen and patient selection, vaccine timing and sequencing, and rational combinations with emerging MM treatments., Competing Interests: HN: Honoraria: Janssen, BMS and Sanofi. FS: Honoraria: Amgen, BMS, Takeda, Abbvie, Janssen, Novartis, SkyliteDX, Oncopeptides, Sanofi, Schain, Pfizer, Daiki-Sankyo; Consultancy: GSK, Celgene, Takeda, Janssen, Oncopeptides, Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Abdollahi, Norseth and Schjesvold.)

Background: Current standard treatment for metastatic breast cancer (MBC) involves cyclin-dependent kinase 4/6 (CDK4/6) inhibitors with endocrine therapy, showing potential in enhancing anti-tumor immune responses., Case Report: This report details a clinical case of MBC where palbociclib was co-administered with letrozole. The integration of allogeneic tumor vaccination to this treatment led to heightened interferon-γ production, expansion of CD8+ and NK cell populations, and positive delayed-type hypersensitivity reactions, indicating successful development of anti-tumor immunity. The induced production of interferon-γ by tumor vaccination was associated with manageable modulation of sensitivity to palbociclib-letrozole therapy. Administration of the BioNTech/Pfizer Covid-19 vaccine compromised the anti-tumor immune response by reducing cytotoxic cell populations and increasing immunosuppressive cytokine production. The patient undergoing combined treatment achieved a progressive-free survival of 42 months., Conclusion: Incorporating active tumor vaccination with CDK4/6 inhibitor therapy presents a feasible approach for metastatic breast cancer. The precise regulation of the microenvironment emerges as a crucial factor and warrants careful consideration., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

CD4 + T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses 1-5 , other CD4 + T cells have recently been implicated in inhibiting this response 6,7 . Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10, granzyme B, perforin, CCL5 and LILRB4. Tumour-specific Tr1 cells suppressed tumour rejection induced by anti-PD1, LDVax or adoptively transferred tumour-specific effector T cells. Mechanistically, HDVax-induced Tr1 cells selectively killed MHC-II tumour antigen-presenting type 1 conventional dendritic cells (cDC1s), leading to low numbers of cDC1s in tumours. We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer., (© 2024. The Author(s).)

Background: The identification of epitope peptides from tumor-associated antigens (TAAs) is informative for developing tumor-specific immunotherapy. However, only a few epitopes have been detected in mouse TAAs of head and neck cancer (HNSCC)., Methods: Novel mouse c-Met-derived T-cell epitopes were predicted by computer-based algorithms. Mouse HNSCC cell line-bearing mice were treated with a c-Met peptide vaccine. The effects of CD8 and/or CD4 T-cell depletion, and vaccine combination with immune checkpoint inhibitors (ICIs) were evaluated. Tumor re-inoculation was performed to assess T-cell memory., Results: We identified c-Met-derived short and long epitopes that elicited c-Met-reactive antitumor CD8 and/or CD4 T-cell responses. Vaccination using these peptides showed remarkable antitumor responses via T cells in which ICIs were not required. The c-Met peptide-vaccinated mice rejected the re-inoculated tumors., Conclusions: We demonstrated that novel c-Met peptide vaccines can induce antitumor T-cell response, and could be a potent immunotherapy in a syngeneic mouse HNSCC model., (© 2024 Wiley Periodicals LLC.)

Cancer nanovaccines represent a promising frontier in cancer immunotherapy, utilizing nanotechnology to augment traditional vaccine efficacy. This review comprehensively examines the current state-of-the-art in cancer nanovaccine development, elucidating innovative strategies and technologies employed in their design. It explores both preclinical and clinical advancements, emphasizing key studies demonstrating their potential to elicit robust anti-tumor immune responses. The study encompasses various facets, including integrating biomaterial-based nanocarriers for antigen delivery, adjuvant selection, and the impact of nanoscale properties on vaccine performance. Detailed insights into the complex interplay between the tumor microenvironment and nanovaccine responses are provided, highlighting challenges and opportunities in optimizing therapeutic outcomes. Additionally, the study presents a thorough analysis of ongoing clinical trials, presenting a snapshot of the current clinical landscape. By curating the latest scientific findings and clinical developments, this study aims to serve as a comprehensive resource for researchers and clinicians engaged in advancing cancer immunotherapy. Integrating nanotechnology into vaccine design holds immense promise for revolutionizing cancer treatment paradigms, and this review provides a timely update on the evolving landscape of cancer nanovaccines., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Immunotherapy has revolutionized cancer treatment by leveraging the immune system's innate capabilities to combat malignancies. Despite the promise of tumor antigens in stimulating anti-tumor immune responses, their clinical utility is hampered by limitations in eliciting robust and durable immune reactions, exacerbated by tumor heterogeneity and immune evasion mechanisms. Recent insights into the immunogenic properties of host homologous microbial antigens have sparked interest in their potential for augmenting anti-tumor immunity while minimizing off-target effects. This review explores the therapeutic potential of microbial antigen peptides in tumor immunotherapy, beginning with an overview of tumor antigens and their challenges in clinical translation. We further explore the intricate relationship between microorganisms and tumor development, elucidating the concept of molecular mimicry and its implications for immune recognition of tumor-associated antigens. Finally, we discuss methodologies for identifying and characterizing microbial antigen peptides, highlighting their immunogenicity and prospects for therapeutic application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Chen, Zhang and Zhang.)

Background: Nanovaccine treatment is an exciting area of research in immunology and personalized medicine, holding great promise for enhancing immune responses and targeting specific diseases. Their small size allows efficient uptake by immune cells, leading to robust immune activation. They can incorporate immune-stimulating molecules to boost vaccine efficacy. Therefore, nanovaccine can be personalized to target tumor-specific antigens, activating the immune system against cancer cells. Currently, there have been ample evidence showing the effectiveness and potential of nanovaccine as a treatment for cancer. However, there was rare bibliometric analysis of nanovaccine for cancer. Here we performed a bibliometric and visual analysis of published studies related to nanovaccine treatment for cancer, providing the trend of future development of nanovaccine., Methods: We collected the literatures based on the Web of Science Core Collection SCI-Expanded database. The bibliometric analysis was performed via utilizing visualization analysis tools VOSviewer, Co-Occurrence (COOC), Citespace, Bibliometrix (R-Tool of R-Studio), and HitCite., Results: A total of 517 literatures were included in this study. China is the country with the most publications and the highest total local citation score (TLCS). The Chinese Academy of Sciences holds the largest research count in this field and the most prolific author is Deling Kong from Nankai University. The most prominent journal for publishing in this area is Biomaterials. The researches mainly focus on the therapeutic process of tumor nanovaccines, the particle composition and the application of nanovaccines, suggesting the potential hotspots and trends of nanovaccine., Conclusion: In this study, we summarized the characteristics and variation trends of publications involved in nanovaccine, and categorized the most influential countries, institutions, authors, journals, hotspots and trends regarding the nanovaccine for cancer. With the continuous development of nanomaterials and tumor immunotherapy, nanovaccine for cancer provides a research field of significant clinical value and potential application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hou, Li, Zhang, Zhang and Wu.)

Exosomes, a subset of extracellular vesicles, are released by all active cells and play a crucial role in intercellular communications. Exosomes could facilitate the transfer of various biologically active molecules, such as DNA, non-coding RNAs, and proteins, from donor to recipient cells, thereby participating in diverse biological and pathological processes. Besides, exosomes possess unique characteristics, including non-toxicity, low-immunogenicity, and stability within biological systems, rendering them highly advantageous for cancer drug development. Meanwhile, accumulating evidence suggests that exosomes originating from tumor cells and immune cells possess distinct composition profiles that play a direct role in anticancer immunotherapy. Of note, exosomes can transport their contents to specific cells, thereby exerting an impact on the phenotype and immune-regulatory functions of targeted cells. Therapeutic cancer vaccines, an emerging therapeutics of immunotherapy, could enhance antitumor immune responses by delivering a large number of tumor antigens, thereby augmenting the immune response against tumor cells. Therefore, the therapeutic rationale of cancer vaccines and exosome-based immunotherapy are almost similar to some extent, but some challenges have hindered their application in the clinical setting. Here, in this review, we first summarized the biogenesis, structure, compositions, and biological functions of exosomes. Then we described the roles of exosomes in cancer biology, particularly in tumor immunity. We also comprehensively reviewed current exosome-based anticancer vaccine development and we divided them into three types. Finally, we give some insights into clinical translation and clinical trial progress of exosome-based anticancer vaccines for future direction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Defective host defenses later in life are associated with changes in immune cell activities, suggesting that age-specific considerations are needed in immunotherapy approaches. In this study, we found that PD-1 and CTLA4-based cancer immunotherapies are unable to eradicate tumors in elderly mice. This defect in anti-tumor activity correlated with two known age-associated immune defects: diminished abundance of systemic naive CD8 + T cells and weak migratory activities of dendritic cells (DCs). We identified a vaccine adjuvant, referred to as a DC hyperactivator, which corrects DC migratory defects in the elderly. Vaccines containing tumor antigens and DC hyperactivators induced T helper type 1 (TH1) CD4 + T cells with cytolytic activity that drive anti-tumor immunity in elderly mice. When administered early in life, DC hyperactivators were the only adjuvant identified that elicited anti-tumor CD4 + T cells that persisted into old age. These results raise the possibility of correcting age-associated immune defects through DC manipulation., Competing Interests: Declaration of interests J.C.K. consults and holds equity in Corner Therapeutics, Larkspur Biosciences, MindImmune Therapeutics, and Neumora Therapeutics. R.J.X. is a co-founder of Celsius and Jnana Therapeutics. None of these relationships impacted this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Immunotherapy is one of the most promising therapeutic approaches in the field of cancer treatment. As a tumor progresses, tumor cells employ an array of immune-regulatory mechanisms to suppress immune responses within the tumor microenvironment. Using our understanding of these mechanisms, cancer immunotherapy has been developed to enhance the immune system's effectiveness in treating cancer. Numerous cancer immunotherapies are currently in clinical use, yet many others are either in different stages of development or undergoing clinical studies. In this paper, we briefly discuss the features and current status of cancer immunotherapies. This includes the application of monoclonal antibodies, immune checkpoint inhibitors, adoptive cell therapy, cytokine therapy, cancer vaccines, and gene therapy, all of which have gained significant recognition in clinical practice. Additionally, we discuss limitations that may hinder successful clinical utilization and promising strategies, such as combining immunotherapy with nanotechnology., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)