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Advanced gastric cancers are responsible for overwhelming human suffering and death. Despite the development of combination chemotherapies, the survival rates of patients with gastric cancer remain unsatisfactory. Given the growing evidence of the benefits of immunotherapy as an alternative treatment for other cancers such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and refractory Hodgkin's lymphoma, researchers have begun to explore its application in the treatment of gastric cancer. Three types of immunotherapy have shown promising effects against gastric cancer: immune checkpoint inhibitors, chimeric antigen rector (CAR)-T cells, and tumor vaccines. Clinical trials have used either immuno-oncology monotherapies or combination immuno-chemotherapies to improve the overall survival times and objective response rates of patients with gastric cancer. We review the clinical efficacy of immunotherapy including checkpoint inhibitors, CAR‑T, and tumor vaccines, in the treatment of gastric cancer. Based on initial evidence, we believe that immunotherapy could positively impact the natural history and improve the outcomes of a subgroup of patients with gastric cancer., (© 2021. Springer Nature Singapore Pte Ltd.)

Chimeric antigen receptor (CAR) T cell therapy has transformed cancer immunotherapy. However, significant challenges limit its application beyond B cell-driven malignancies, including limited clinical efficacy, high toxicity, and complex autologous cell product manufacturing. Despite efforts to improve CAR T cell therapy outcomes, there is a growing interest in utilizing alternative immune cells to develop CAR cells. These immune cells offer several advantages, such as major histocompatibility complex (MHC)-independent function, tumor microenvironment (TME) modulation, and increased tissue infiltration capabilities. Currently, CAR products from various T cell subtypes, innate immune cells, hematopoietic progenitor cells, and even exosomes are being explored. These CAR products often show enhanced antitumor efficacy, diminished toxicity, and superior tumor penetration. With these benefits in mind, numerous clinical trials are underway to access the potential of these innovative CAR cells. This review aims to thoroughly examine the advantages, challenges, and existing insights on these new CAR products in cancer treatment. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor-T (CAR-T) cell therapy based on functional immune cell transfer is showing a booming situation. However, complex manufacturing processes, high costs, and disappointing results in the treatment of solid tumors have limited its use. Encouragingly, it has facilitated the development of new strategies that fuse immunology, cell biology, and biomaterials to overcome these obstacles. In recent years, CAR-T engineering assisted by properly designed biomaterials has improved therapeutic efficacy and reduced side effects, providing a sustainable strategy for improving cancer immunotherapy. At the same time, the low cost and diversity of biomaterials also offer the possibility of industrial production and commercialization. Here, we summarize the role of biomaterials as gene delivery vehicles in the generation of CAR-T cells and highlight the advantages of in-situ construction in vivo. Then, we focused on how biomaterials can be combined with CAR-T cells to better enable synergistic immunotherapy in the treatment of solid tumors. Finally, we describe biomaterials' potential challenges and prospects in CAR-T therapy. This review aims to provide a detailed overview of biomaterial-based CAR-T tumor immunotherapy to help investigators reference and customize biomaterials for CAR-T therapy to improve the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

T cell-based immunotherapy has demonstrated great therapeutic potential in recent decades, on the one hand, by using tumor-infiltrating lymphocytes (TILs) and, on the other hand, by engineering T cells to obtain anti-tumor specificities through the introduction of either engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs). Given the distinct design of both receptors and the type of antigen that is encountered, the requirements for proper antigen engagement and downstream signal transduction by TCRs and CARs differ. Synapse formation and signal transduction of CAR T cells, despite further refinement of CAR T cell designs, still do not fully recapitulate that of TCR T cells and might limit CAR T cell persistence and functionality. Thus, deep knowledge about the molecular differences in CAR and TCR T cell signaling would greatly advance the further optimization of CAR designs and elucidate under which circumstances a combination of both receptors would improve the functionality of T cells for cancer treatment. Herein, we provide a comprehensive review about similarities and differences by directly comparing the architecture, synapse formation and signaling of TCRs and CARs, highlighting the knowns and unknowns. In the second part of the review, we discuss the current status of combining CAR and TCR technologies, encouraging a change in perspective from "TCR versus CAR" to "TCR and CAR". [ABSTRACT FROM AUTHOR]

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR+ T cells effector functions in terms of antigen-specific cytotoxicity, cytokine release and proliferation. Overall, lenalidomide preserved functional CAR T-CLL cell immune synapses. In a Rag2−/−γc−/−-based xenograft model of CLL, we demonstrated that, when combined with low-dose lenalidomide, CD23.CAR+ T cells efficiently migrated to leukemic sites and delayed disease progression when compared to CD23.CAR+ T cells given with rhIL-2. These observations underline the therapeutic potential of this novel CAR-based combination strategy in CLL. [ABSTRACT FROM AUTHOR]

Current Therapeutic modalities provide no survival advantage to gastric cancer (GC) patients. Targeting the human epidermal growth factor receptor-2 (HER-2) is a viable therapeutic strategy against advanced HER-2 positive GC. Antibody-drug conjugates, small-molecule tyrosine kinase inhibitors (TKIs), and bispecific antibodies are emerging as novel drug forms that may abrogate the resistance to HER-2-specific drugs and monoclonal antibodies. Chimeric antigen receptor-modified T cells (CAR-T) targeting HER-2 have shown considerable therapeutic potential in GC and other solid tumors. However, due to the high heterogeneity along with the complex tumor microenvironment (TME) of GC that often leads to immune escape, the immunological treatment of GC still faces many challenges. Here, we reviewed and discussed the current progress in the research of anti-HER-2-CAR-T cell immunotherapy against GC. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading cause of death in human beings throughout the world. Attempts to treat cancer are made but not effectively. Surgical removal, use of radiation therapy, chemotherapy and combination of these therapies have been tried to cure cancer but every therapy had its own side effects. Due to potential side effects, these therapies failed to develop as the permanent cure for cancer. Stem cell transplantation has also been attempted as an alternative but the recovery rate was very low. The most recent therapy, nowadays, to treat cancer is immunotherapy in which utilises the immunity of the patient to get modulated in such a way that cancerous cells get killed. So this review enlightens the eminent immunotherapies used for veterinary patients. T cell checkpoint inhibitors, engineered T cells, cancer vaccines and anti-B and anti-T cell antibodies are amongst the important immunotherapies used in human as well as veterinary patient. Inhibition of T cell checkpoint molecules, such as PD-1 and CTLA-4, using monoclonal antibodies are the most advanced techniques developed in humans. These significant immunotherapies have achieved notable success against some of the advanced tumors in humans, including melanoma, renal cell carcinoma and non small cell lung cancer. However, a recent clinical trial with a caninized monoclonal antibody against canine PD-L1 showed response in canine melanoma. [ABSTRACT FROM AUTHOR]

Immunotherapy has established itself as a promising tool for cancer treatment. There are many challenges that remain including lack of targets and some patients across various cancers who have not shown robust clinical response. One of the major problems that have hindered the progress in the field is the dearth of appropriate mouse models that can reliably recapitulate the complexity of human immune-microenvironment as well as the malignancy itself. Immunodeficient mice reconstituted with human immune cells offer a unique opportunity to comprehensively evaluate immunotherapeutic strategies. These immunosuppressed and genetically modified mice, with some overexpressing human growth factors, have improved human hematopoietic engraftment as well as created more functional immune cell development in primary and secondary lymphoid tissues in these mice. In addition, several new approaches to modify or to add human niche elements to further humanize these immunodeficient mice have allowed a more precise characterization of human hematopoiesis. These important refinements have opened the possibility to evaluate not only human immune responses to different tumor cells but also to investigate how malignant cells interact with their niche and most importantly to test immunotherapies in a more preclinically relevant setting, which can ultimately lead to better success of these drugs in clinical trials. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a malignant tumor that negatively impacts human health, which typically presents in the advanced stages of disease in the majority of patients. Despite the development of combination chemotherapy, only a modest survival advantage is gained in patients with GC treated by this method. Recently, cancer immunotherapies have received considerable attention as a viable therapeutic option for GC. Specifically, the immune checkpoint inhibitors, chimeric antigen rector (CAR)-T cells and tumor vaccines, represent immunotherapies that have exhibited promising effects in the treatment of GC. A number of clinical trials have employed either immuno-oncology monotherapies or combination therapies to improve the overall survival time (OS) and objective response rate (ORR) of patients with GC. The current review presents a summary of the clinical effects of checkpoint inhibitors, including CAR-T and tumor vaccines, in the treatment of GC. [ABSTRACT FROM AUTHOR]

Immunotherapy holds tremendous promise for improving cancer treatment in which an appropriate stimulator may naturally trigger the immune system to control cancer. Up-to-date, adoptive T-cell therapy has received two new FDA approvals that provide great hope for some cancer patient groups. Nevertheless, expense and safety-related issues require further study to obtain insight into targets for efficient immunotherapy. The development of material science was largely responsible for providing a promising horizon to strengthen immunoengineering. In this review, we focus on T-cell characteristics in the context of the immune system against cancer and discuss several approaches of exploiting engineered particles to manipulate the responses of T cells and the tumour microenvironment. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects. [ABSTRACT FROM AUTHOR]

The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor-modified T-cell immunotherapy (CAR-T) and programmed cell death protein-1 blockade (PD-1 blockade). CAR-T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients. PD-1 blockade has been reported to exert marked clinical responses in patients against a range of types of solid cancer, including advanced melanoma, non-small-cell lung cancer and renal cell carcinoma, in addition to hematological malignancies. While increasing the power of the immune system to fight cancer has been a long-standing goal in oncology, a number of studies have demonstrated the synergistic antitumor effects of combination therapies under the umbrella of immunotherapy. The present review focused on a novel combination approach involving CAR-T and PD-1 blockade. The present reviews aimed to discuss the following four aspects of such an approach: i) Current monotherapy status; ii) rationale for the combination of CAR-T and PD-1 blockade; iii) current status of the combination of CAR-T and PD-1 blockade; and iv) conclusions and future perspectives. [ABSTRACT FROM AUTHOR]

Gene-engineered T-cell therapies have the potential to revolutionize the treatment of cancer. These therapies have shown exceptional clinical efficacy specifically in the field of B-cell malignancies and the first products (Kymriah™ and Yescarta™) have recently been approved in the United States for specific indications. The power of these treatments is also linked with a distinct set of toxicities both predicted and unpredicted, including off-tumor activity, cytokine release syndromes, and neurotoxicity, occasionally with fatal consequences. As these therapies begin to reach more patients, it is critical to develop the nonclinical tools to adequately determine the mechanisms driving these toxicities, to assess the safety risks of candidate products, and to develop strategies for safety management. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. Methods: We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific singlechain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-? signaling domain. We further investigate the function of CLL-1 CAR-T cells. Results: The CLL-1 CAR-T cells specifically lysed CLL-1+ cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1+ myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. Conclusions: CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML. [ABSTRACT FROM AUTHOR]

Adoptive transfer of chimeric antigen receptor-engineered T cells (CARTs) is a novel approach to cancer therapy as CARTs combine with the antigen specificity of an antibody and the activating functions of T lymphocytes. Recent results from preclinical and clinical trials with CARTs for B-cell malignancies are exciting, although different groups selected different tumor-associated antigens, binding domains, and signal domains, which make up the chimeric antigen receptor (CAR) configuration. However, there are few clinical trials with CARTs for solid tumors compared to hematologic malignancies. In this brief review, we discuss the basic principles of CAR design and clinical studies of CARTs for solid tumors. [ABSTRACT FROM AUTHOR]

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. [ABSTRACT FROM AUTHOR]

It is now well established that the immune system can control and eliminate cancer cells. Adoptive T cell transfer has the potential to overcome the significant limitations associated with vaccine-based strategies in patients who are often immune compromised. Application of the emerging discipline of synthetic biology to cancer, which combines elements of genetic engineering and molecular biology to create new biological structures with enhanced functionalities, is the subject of this overview. Various chimeric antigen receptor designs, manufacturing processes and study populations, among other variables, have been tested and reported in recent clinical trials. Many questions remain in the field of engineered T cells, but the encouraging response rates pave a wide road for future investigation into fields as diverse as cancer and chronic infections. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy comprises different therapeutic strategies that exploit the use of distinct components of the immune system, with the common goal of specifically targeting and eradicating neoplastic cells. These varied approaches include the use of specific monoclonal antibodies, checkpoint inhibitors, cytokines, therapeutic cancer vaccines and cellular anticancer strategies such as activated dendritic cell (DC) vaccines, tumor-infiltrating lymphocytes (TILs) and, more recently, genetically engineered T cells. Each one of these approaches has demonstrated promise, but their generalized success has been hindered by the paucity of specific tumor targets resulting in suboptimal tumor responses and unpredictable toxicities. This review will concentrate on recent advances on the use of engineered T cells for adoptive cellular immunotherapy (ACI) in cancer. [ABSTRACT FROM AUTHOR]

The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise novel strategies that exploit the patient's immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematologic malignancies, including (i) conventional monoclonal therapies like rituximab; (ii) engineered monoclonal antibodies called bispecific T-cell engagers; (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4, and IDO); and (iv) adoptive cell transfer therapy with T cells engineered to express chimeric antigen receptors or T-cell receptors. We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. [ABSTRACT FROM AUTHOR]

Multi-agent chemotherapy is the standard treatment for most B cell malignancies. Since chemotherapy can be associated with significant toxicity and since relapses resistant to chemotherapy often develop, new therapies are needed. Blinatumomab (AMG 103 or MT103) is a late-stage candidate in clinical development, which belongs to a novel class of antibody constructs termed bi-specific T cell engager antibodies. This antibody construct has dual specificity for CD19 and CD3 and can re-direct polyclonal cytotoxic T lymphocytes toward the tumor. This review focuses on the pre-clinical and clinical development of blinatumomab as a powerful new tool in the treatment of B cell malignancies. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB), accounting for 10% of childhood cancers, exhibits aberrant cell-surface glycosylation patterns. There is evidence that changes in glycolipids and protein glycosylation pathways are associated to NB biological behavior. Polysialic acid (PSA) inter-feres with cellular adhesion, and correlates with NB progression and poor prognosis, as well as the expression of sialyltransferase STX, the key enzyme responsible for PSA synthesis. Galectin-1 and gangliosides, overexpressed and actively shedded by tumor cells, can modulate normal cells present in the tumor microenvironment, favoring angiogenesis and immunological escape. Different glycosyltransferases are emerging as tumor markers and potential molecular targets. Immunotherapy targeting disialoganglioside GD2 rises as an important treatment option. One anti-GD2 antibody (ch14.18), combined with IL-2 and GM-CSF, significantly improves survival for high-risk NB patients. This review summarizes our current knowledge on NB glycobiology, highlighting the molecular basis by which car-bohydrates and protein-carbohydrate interactions impact on biological behavior and patient clinical outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptors (CARs) targeting CD19 have emerged as a new treatment for hematological malignancies. As a "living therapy", CARs can precisely target and eliminate tumors while proliferating inside the patient's body. Various preclinical and clinical studies are ongoing to identify potential CAR-T cell targets for acute myeloid leukemia (AML). We shed light on the continuing efforts of CAR development to overcome tumor escape, exhaustion, and toxicities. Furthermore, we summarize the recent progress of a range of putative targets exploring this unmet need to treat AML. Lastly, we discuss the advances in preclinical models that built the foundation for ongoing clinical trials. Engineered T cells expressing chimeric antigen receptors (CARs) on their cell surface can redirect antigen specificity. This ability makes CARs one of the most promising cancer therapeutic agents. CAR-T cells for treating patients with B cell hematological malignancies have shown impressive results. Clinical manifestation has yielded several trials, so far five CAR-T cell therapies have received US Food and Drug Administration (FDA) approval. However, emerging clinical data and recent findings have identified some immune-related toxicities due to CAR-T cell therapy. Given the outcome and utilization of the same proof of concept, further investigation in other hematological malignancies, such as leukemias, is warranted. This review discusses the previous findings from the pre-clinical and human experience with CAR-T cell therapy. Additionally, we describe recent developments of novel targets for adoptive immunotherapy. Here we present some of the early findings from the pre-clinical studies of CAR-T cell modification through advances in genetic engineering, gene editing, cellular programming, and formats of synthetic biology, along with the ongoing efforts to restore the function of exhausted CAR-T cells through epigenetic remodeling. We aim to shed light on the new targets focusing on acute myeloid leukemia (AML). [ABSTRACT FROM AUTHOR]

Simple Summary: There is still no effective treatment for advanced prostate cancer. CAR-T therapy is a promising approach; however, many obstacles remain for the treatment of solid tumors due to the complex physical barriers and inhibitory microenvironment in solid tumors. Single CAR-T therapy has a low response rate and a high recurrence rate. With the enhancement of CAR-T itself and the gradual improvement of the immune microenvironment, the number of CAR-T weapons against tumors is increasing. This article discusses the current status and future of CAR-T therapy for prostate cancer. We believe that the enhancement and modification of CAR-T or CAR-T combined with other therapies are expected to be a breakthrough in the treatment of prostate cancer. The incidence rate of prostate cancer is higher in male cancers. With a hidden initiation of disease and long duration, prostate cancer seriously affects men's physical and mental health. Prostate cancer is initially androgen-dependent, and endocrine therapy can achieve good results. However, after 18–24 months of endocrine therapy, most patients eventually develop castration-resistant prostate cancer (CRPC), which becomes metastatic castration resistant prostate cancer (mCRPC) that is difficult to treat. Chimeric Antigen Receptor T cell (CAR-T) therapy is an emerging immune cell therapy that brings hope to cancer patients. CAR-T has shown considerable advantages in the treatment of hematologic tumors. However, there are still obstacles to CAR-T treatment of solid tumors because the physical barrier and the tumor microenvironment inhibit the function of CAR-T cells. In this article, we review the progress of CAR-T therapy in the treatment of prostate cancer and discuss the prospects and challenges of armed CAR-T and combined treatment strategies. At present, there are still many obstacles in the treatment of prostate cancer with CAR-T, but when these obstacles are solved, CAR-T cells can become a favorable weapon for the treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Effective cancer immunotherapies, with the objective to boost tumor-specific immune responses, is a game-changer in personalized cancer treatment. In immunotherapy, the immune system is exploited to recognize and destroy cancer cells, and this is only possible if a full recapitulation of tumor specific antigens complexity is achieved. Patient-derived induced pluripotent stem cells (iPSCs) share several characteristics with cancer (stem) cells (CSCs). The exploitation of iPSCs as a source of tumor- and patient-specific antigens guiding the immune system against cancer has been addressed recently in mice. Here, we will debate novel findings on the potential implication of cellular reprogramming and iPSCs plasticity for the design of novel cancer immunotherapeutic strategies. Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunotherapy has emerged as a pioneering and promising approach for cancer therapy and management, and in particular intended for advanced tumors unresponsive to current therapeutics. In cancer immunotherapy, components of the immune system are exploited to eliminate cancer cells and treat patients. The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer treatment. Despite their potential success, current approaches depend on efficient tumor antigen presentation which are often inaccessible, and most tumors turn refractory to current immunotherapy. Patient-derived induced pluripotent stem cells (iPSCs) have been shown to share several characteristics with cancer (stem) cells (CSCs), eliciting a specific anti-tumoral response when injected in rodent cancer models. Indeed, artificial cellular reprogramming has been widely compared to the biogenesis of CSCs. Here, we will discuss the state-of-the-art on the potential implication of cellular reprogramming and iPSCs for the design of patient-specific immunotherapeutic strategies, debating the similarities between iPSCs and cancer cells and introducing potential strategies that could enhance the efficiency and therapeutic potential of iPSCs-based cancer vaccines. [ABSTRACT FROM AUTHOR]

CAR-T (chimeric antigen receptor T cells) immunotherapy is effective in many hematological cancers; however, efficacy in solid tumors is disappointing. Doublecortin-like kinase 1 (DCLK1) labels tumor stem cells (TSCs) in genetic mouse models of colorectal cancer (CRC). Here, we describe a novel CAR-T targeting DCLK1 (CBT-511; with our proprietary DCLK1 single-chain antibody variable fragment) as a treatment strategy to eradicate CRC TSCs. The cell surface expression of DCLK1 and cytotoxicity of CBT-511 were assessed in CRC cells (HT29, HCT116, and LoVo). LoVo-derived tumor xenografts in NOD Scid gamma (NSG™) mice were treated with CBT-511 or mock CAR-T cells. Adherent CRC cells express surface DCLK1 (two-dimensional, 2D). A 4.5-fold increase in surface DCLK1 was observed when HT29 cells were grown as spheroids (three-dimensional, 3D). CBT-511 induced cytotoxicity (2D; p < 0.0001), and increased Interferon gamma (IFN-γ) release in CRC cells (2D) compared to mock CAR-T (p < 0.0001). Moreover, an even greater increase in IFN-γ release was observed when cells were grown in 3D. CBT-511 reduced tumor growth by approximately 50 percent compared to mock CAR-T. These data suggest that CRC cells with increased clonogenic capacity express increased surface DCLK1. A DCLK1-targeted CAR-T can induce cytotoxicity in vitro and inhibit xenograft growth in vivo. [ABSTRACT FROM AUTHOR]

Given the success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells in clinical settings, the host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy. As a result, there have been numerous advancements in immune cell therapy using human immune cells. However, recent evidence suggests that one type of immunotherapy alone is not effective for the treatment of cancer, particularly solid tumors. Thus, effective immunotherapy combinations, such as the combination of checkpoint inhibitors and immune cell therapy, are needed. This review focuses on hepatocellular carcinoma among other solid tumors and discusses the current status and future of immune cell therapy in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

We have engineered a novel fusion cytokine named GIFT4 derived from GM-CSF and IL-4, and displaying robust gain-of-function immunostimulatory effects on B cells. GIFT4-programmed B cells have a unique identity and potent capacity to elicit a tumoricidal - cell response, thus comprising a novel B cell-based cancer immunotherapeutic approach. [ABSTRACT FROM AUTHOR]