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Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identifying new tumour-specific antigens to design new generations of cancer vaccines with high specificity and long-term efficacy. Furthermore, combinatorial regimens of cancer vaccines with immune checkpoint inhibitors have offered new therapeutic approaches and demonstrated impressive efficacy in cancer patients over the last few years. In the present review, we summarize the current state of cancer vaccines, including their potential therapeutic effects and the limitations that hinder their effectiveness. We highlight the current efforts to mitigate these limitations and highlight ongoing clinical trials. Finally, a special focus will be given to the latest milestones expected to transform the landscape of cancer therapy and nurture hope among cancer patients. [ABSTRACT FROM AUTHOR]

Screening for effective vaccines requires broad studies on their immunogenicity in vitro and ex vivo. We used a PBMC-based system to assess changes in CD4+ T cells, CD8+ T cells, and CD19+ B cells upon stimulation with different combinations of antigens and adjuvants. We studied the activation mechanism using flow cytometry and two different adenoviral adjuvants characterized by the presence or absence of costimulatory ligands for the ICOS and CD40 receptors. Our studies identified the cellular targets and molecular mechanisms driving ongoing switched-antibody diversification. Class-switched memory B cells were the main precursor cells (95.03% ± 0.38 vs. mock 82.33% ± 0.45, P < 0.05) after treatment with the immunogenic formula: adenovirus armed (MIX1) or not (MIX2) with the ICOS and CD40 ligand, the recombinant receptor binding domain (rRBD), and Lentifect™ SARS-CoV-2 spike-pseudotyped lentivirus (GeneCopoeia, USA). Bcell class-switching towards the IgG+IgM+- positive phenotypes was noted (-50-fold increase vs. mock, P < 0.05). A significant increase was observed in the CD8+TEM population of the MIX1 (-2-fold, P < 0.05) and MIX2 (-4.7-fold, P < 0.05) treated samples. CD8+TEMRA increased when PBMCs were treated with MIX2 (9.63% ± 0.90, P < 0.05) vs. mock (2.63% ± 1.96). Class-switched memory B cells were the dominant antigen-specific cells in primary reactions. We indicated a correlation between the protection offered by vaccine regimens and their ability to induce high frequencies of multifunctional T cells. [ABSTRACT FROM AUTHOR]

The challenge of integrating hydroxyapatite nanoparticles (nHAp) with polymers is hindered by the conflict between the hydrophilic and hygroscopic properties of nHAp and the hydrophobic properties of polymers. This conflict particularly affects the materials when calcium phosphates, including nHAp, are used as a filler in composites in thermal processing applications such as 3D printing with fused filament fabrication (FFF). To overcome this, we propose a one‐step surface modification of nHAp with calcium stearate monolayer. Moreover, to build the scaffold with suitable mechanical strength, we tested the addition of nHAp with diverse morphology—spherical, plate‐ and rod‐like nanoparticles. Our analysis showed that the composite of polycaprolactone (PCL) reinforced with nHAp with rod and plate morphologies modified with calcium stearate monolayer exhibited a significant increase in compressive strength. However, composites with spherical nHAp added to PCL showed a significant reduction in compressive modulus and compressive strength, but both parameters were within the applicability range of hard tissue scaffolds. None of the tested composite scaffolds showed cytotoxicity in L929 murine fibroblasts or MG‐63 human osteoblast‐like cells, supporting the proliferation of the latter. Additionally, PCL/nHAp scaffolds reinforced with spherical nHAp caused osteoactivation of bone marrow human mesenchymal stem cells, as indicated by alkaline phosphatase activity and COL1, RUNX2, and BGLAP expression. These results suggest that the calcium stearate monolayer on the surface of the nHAp particles allows the production of polymer/nHAp composites suitable for hard tissue engineering and personalized implant production in 3D printing using the FFF technique. [ABSTRACT FROM AUTHOR]

New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes. Adenovirus AdV2 (adjuvant), without ligands, in combination with rRBD, served as a control. In vitro T-cell responses to the AdV1+rRBD combination revealed that CD8+ platform-specific T-cells increased (37.2 ± 0.7% vs. 23.1 ± 2.1%), and T-cells acted against SARS-CoV-2 via CD8+TEMRA (50.0 ± 1.3% vs. 36.0 ± 3.2%). Memory B cells were induced after treatment with either AdV1+rRBD (84.1 ± 0.8% vs. 82.3 ± 0.4%) or rRBD (94.6 ± 0.3% vs. 82.3 ± 0.4%). Class-switching from IgM and IgD to isotype IgG following induction with rRBD+Ab was observed. RNA-seq profiling identified gene expression patterns related to T helper cell differentiation that protect against pathogens. The analysis determined signaling pathways controlling the induction of protective immunity, including the MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor signaling pathway. The AdV1+rRBD formulation induced IL-6, IL-8, and TNF. RNA-seq of the VERO E6 cell line showed differences in the apoptosis gene expression stimulated with the platforms vs. mock. In conclusion, AdV1+rRBD effectively generates T and B memory cell-mediated protection, presenting promising results in producing CD8+ platform-specific T cells and isotype-switched IgG memory B cells. The platform induces protective immunity by controlling the Th1, Th2, and Th17 cell differentiation gene expression patterns. Further studies are required to confirm its effectiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: Current cancer therapies are insufficient to cure advanced malignancies and cause off-target toxicity. Scientists have focused on developing new, more efficacious, and selective therapies to overcome these issues. This review describes a modern approach based on oncotherapy, a type of cancer treatment that helps the immune system fight cancer. Thus, genetic modifications of adenoviruses to increase the anticancer properties of the therapy (benefits, critical points, and risk assessment) were reviewed. We analyzed clinical trial databases and highlighted significant achievements in adenovirus oncotherapy in recent years. In clinical trials, adenovirus vectors (AdVs) are commonly used platforms for human gene delivery therapy. High genome capacity and flexibility in gene organization make HAdVs suitable for cloning. Recent advancements in molecular techniques have influenced the development of genetically engineered adenovirus vectors showing therapeutic potential. Increased molecular understanding of the benefits and limitations of HAdVs in preclinical research and clinical studies is a crucial point in the engineering of refined oncolytic vectors. This review presents HAdV species (A–G) used in oncotherapy. We describe the adenovirus genome organizations and modifications, the possibilities oncolytic viruses offer, and their current limitations. Ongoing and ended clinical trials based on oncolytic adenoviruses are presented. This review provides a broad overview of the current knowledge of oncolytic therapy. HAdV-based strategies targeting tumors by employing variable immune modifiers or delivering immune stimulatory factors are of great promise in the field of immune oncologyy This approach can change the face of the fight against cancer, supplying the medical tools to defeat tumors more selectively and safely. [ABSTRACT FROM AUTHOR]