Tumor-specific Antigens Research Articles

Key Considerations for a Prostate Cancer mRNA Vaccine.

Prostate cancer has the second highest cancer mortality rate in the UK in males. Early prostate cancer is typically asymptomatic, with diagnosis at a locally advanced or metastatic stage. In addition, the inherent heterogeneity of prostate cancer tumours differs significantly in terms of genetic, molecular, and histological features. The successful treatment of prostate cancer is therefore exceedingly challenging. Immunotherapies, particularly therapeutic vaccines, have been widely used in preclinical and clinical studies to treat various cancers. Sipuleucel-T was the first cancer vaccine approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), ushering in a new era of immunotherapy. In this review, the latest immunotherapy strategies for prostate cancer are considered with key tumour-associated antigens (TAA) and tumour-specific antigens (TSA) highlighted. The key components of mRNA vaccines include in vitro transcription, stability, and immunogenicity. Finally, strategies to circumvent in vivo mRNA degradation and approaches to optimise in vitro transcription (IVT) process are also discussed.

ATAD2 is a potential immunotherapy target for patients with small cell lung cancer harboring HLA-A∗0201.

Small cell lung cancer (SCLC) represents a highly aggressive neuroendocrine tumour with a dismal prognosis. Currently, the identification of a specific tumour antigen that can facilitate immune-based therapies for SCLC remains elusive. We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyse cancer/testis antigens (CTAs) in SCLC cell lines and human tumour specimens. Immunohistochemistry of clinical specimens was performed to compare protein expression in SCLC, non-small cell lung cancer (NSCLC), and matched normal-adjacent tissues. Additionally, publicly available RNA sequencing databases were interrogated to identify gene expression patterns in different SCLC subtypes and in different disease stages. Distinct numbers and types of CTAs were identified across SCLC subtypes, with significantly higher expression levels of ATPase family AAA domain-containing protein 2 (ATAD2) observed in SCLC compared to normal adjacent tissues and NSCLC tissues. A dynamic expression pattern of ATAD2 was found throughout the clinical course of SCLC and exhibited a positive correlation with achaete-scute family bHLH transcription factor 1 (ASCL1) expression in SCLC. Immunopeptidomics analysis identified the YSDDDVPSV sequence derived from the HLA-A∗02:01 restriction epitope of ATAD2 as a highly promising tumour antigen candidate for potential immunotherapy applications. YSDDDVPSV immunopeptides were confirmed to be present in SCLC-A and SCLC-N with HLA-A∗02:01 restriction. Notably, HLA-A∗02:01T cells exhibited a robust response upon stimulation with YSDDDVPSV immunopeptide pulsed by T2 cells. Our findings highlight the potential of targeting the ATAD2 YSDDDVPSV immunopeptide for SCLC immunotherapy, thereby offering a promising avenue for the development of adoptive T cell therapies to effectively treat ASCL1-positive or NEUROD1-positive SCLC carrying HLA-A∗02:01. This study was supported by the National key R&D program of China (2022YFC2505000); National Natural Science Foundation of China (NSFC) general program (82272796) NSFC special program (82241229); CAMS Innovation Fund for Medical Sciences (CIFMS 2022-I2M-1-009); CAMS Key Laboratory of Translational Research on Lung Cancer (2018PT31035); Aiyou foundation (KY201701). National key R&D program of China (2022YFC2505004). NSFC general program (81972905). Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MOCP2022012).

Recent advances in immunotherapy for cervical cancer.

Cervical cancer is the third most common malignant tumor in women worldwide in terms of both incidence and mortality. The field of cervical cancer treatment is rapidly evolving, and various combination therapies are being explored to enhance the efficacy of immune checkpoint inhibitors (ICI) and provide new treatment options for patients at different disease stages. Clinical trials involving immune checkpoint inhibitors are now being conducted following a phase 3 trial with cemiplimab, an ICI, which demonstrated a significant improvement in prognosis in advanced or metastatic cervical cancer patients. These trials include monotherapy and combination therapy with other immune therapies, chemotherapy, or radiation therapy. Furthermore, other approaches for controlling tumors via the immune system, such as therapeutic vaccination for specific tumor antigens or immune cell therapy including chimeric antigen receptor (CAR)-T cell therapy and tumor-infiltrating lymphocytes are being investigated. Ongoing trials will continue to illuminate the optimal strategies for combining these therapies and addressing challenges associated with immune checkpoint failure in cervical cancer. Herein, we conducted a review of articles related to immunotherapy for cervical cancer and describe current treatment strategies for cervical cancer via immunotherapy.

A Bi-Specific T Cell-Engaging Antibody Shows Potent Activity, Specificity, and Tumor Microenvironment Remodeling in Experimental Syngeneic and Genetically Engineered Models of GBM.

Bispecific T cell-engagers (BTEs) are engineered antibodies that redirect T cells to target antigen-expressing tumors. BTEs targeting tumor-specific antigens such as interleukin 13 receptor alpha 2 (IL13Rα2) and EGFRvIII have been developed for glioblastoma (GBM). However, there is limited mechanistic understanding of the action of BTE since prior studies were mostly conducted in immunocompromised animal models. To close this gap, the function of BTEs was assessed in the immunosuppressive glioma microenvironment (TME) of orthotopic and genetically engineered mouse models (GEMM) with intact immune systems. A BTE that bridges CD3 epsilon on murine T cells to IL13Rα2-positive GBM cells was developed and the therapeutic mechanism investigated in immunocompetent mouse models of GBM. Multi-color flow cytometry, single-cell RNA sequencing (scRNA-Seq), multiplex immunofluorescence, and multiparametric magnetic resonance imaging (MRI) across multiple pre-clinical models of GBM were used to evaluate the mechanism and action and response. BTE-mediated interactions between murine T cells and GBM cells triggered T cell activation and antigen-dependent killing of GBM cells. BTE treatment significantly extended the survival of mice bearing IL13Rα2-expressing orthotopic glioma and de novo forming GBM in the GEMM. Quantified parametric MR imaging validated the survival data showing a reduction in glioma volume and decreased glioma viability. Flow cytometric and scRNA-seq analyses of the TME revealed robust increases in activated and memory T cells and decreases in immunosuppressive myeloid cells in the brains of mice following BTE treatment. Our data demonstrate that the survival benefits of BTEs in preclinical models of glioma are due to the ability to engage the host immune system in direct killing, induction of immunological memory, and modulation of the TME. These findings provide a deeper insight into the mechanism of BTE actions in GBM.

A new weapon: the application of tumor vaccines based on extracellular exosomal heat shock proteins in immunotherapy

Despite the significant advancements in cancer research, innovative approaches are still needed to reduce tumor incidence, progression, and dissemination, as well as for prolonging patient survival. Currently, the development of cancer vaccines is gaining attention as a novel preventative and therapeutic strategy. Although the concept of cancer vaccination is not new, a limited number of vaccines have received approval for tumor therapy. Heat shock protein (HSP)-based vaccination represents a promising strategy that harnesses specific tumor antigens to activate immune responses. Exosomes (Exs) are highly heterogeneous bilayer vesicles capable of transporting various types of molecules through extracellular space. Compared with conventional anticancer drugs, exosomes exhibit low toxicity and good biocompatibility, and they can stimulate the immune system either directly or indirectly. Ex-based vaccines may elicit an antitumor immune response that generates memory cells capable of recognizing cancer antigens, thereby inhibiting disease progression. This paper reviews the potential applications of HSPs and exosomes in the prevention and treatment of solid tumors. Finally, we discuss the advantages of the extracellular exosomal heat shock protein (HSP-Ex1) vaccine and future research directions aimed at optimizing heat shock protein-based cancer immunotherapy strategies.

Triple knockdown of CD11a, CD49d, and PSGL1 in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice.

Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue. Here, we demonstrated that targeting the cell adhesion and migration molecules lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) and very late activation antigen 4 (VLA-4; CD49d/CD29) with blocking antibodies reduced the on-target, off-tumor toxicity of CAR-T cells in mice. To translate this observation into improved CAR-T cell therapy, we either knocked out both CD11a and CD49d or knocked down CD11a and CD49d along with PSGL1, another cell adhesion molecule, in CAR-T cells. We found that these modified CAR-T cells exhibited reduced on-target, off-tumor toxicity in vivo without affecting CAR-T cell efficacy. Furthermore, we showed that this approach promoted T cell memory formation and decreased tonic signaling. On the basis of these data, we engineered a human version of these low-toxicity CAR-T cells and further validated the feasibility of this approach in vitro and in vivo. Together, these results provide a potential solution to address the clinical challenge of on-target, off-tumor toxicity in CAR-T therapy.

Characterization of Tumor Antigens from Multi-omics Data: Computational Approaches and Resources.

Tumor-specific antigens, also known as neoantigens, have potential utility in anti-cancer immunotherapy, including immune checkpoint blockade (ICB), neoantigen-specific T cell receptor-engineered T (TCR-T), chimeric antigen receptor T (CAR-T), and therapeutic cancer vaccines (TCVs). After recognizing presented neoantigens, the immune system becomes activated and triggers the death of tumor cells. Neoantigens may be derived from multiple origins, including somatic mutations (single nucleotide variants, insertion/deletions, and gene fusions), circular RNAs, alternative splicing, RNA editing, and polymorphic microbiome. An increasing amount of bioinformatics tools and algorithms are being developed to predict tumor neoantigens derived from different sources, which may require inputs from different multi-omics data. In addition, calculating the peptide-major histocompatibility complex (MHC) affinity can aid in selecting putative neoantigens, as high binding affinities facilitate antigen presentation. Based on these approaches and previous experiments, many resources were developed to reveal the landscape of tumor neoantigens across multiple cancer types. Herein, we summarized these tools, algorithms, and resources to provide an overview of computational analysis for neoantigen discovery and prioritization, as well as the future development of potential clinical utilities in this field.

The Immune-Genomics of Cholangiocarcinoma: A Biological Footprint to Develop Novel Immunotherapies.

Cholangiocarcinoma (CCA) represents approximately 3% of all gastrointestinal cancers and is a highly heterogeneous and aggressive malignancy originating from the epithelial cells of the biliary tree. CCA is classified by anatomical location into intrahepatic (iCCA), extrahepatic (eCCA), gallbladder cancer (GBC), and ampullary cancers. Although considered a rare tumor, CCA incidence has risen globally, particularly due to the increased diagnosis of iCCA. Genomic and immune profiling studies have revealed significant heterogeneity within CCA, leading to the identification of molecular subtypes and actionable genetic alterations in 40-60% of cases, particularly in iCCA. Among these, FGFR2 rearrangements or fusions (7-15%) and IDH1 mutations (10-20%) are common in iCCA, while HER2 amplifications/overexpression are more frequent in eCCA and GBC. The tumor-immune microenvironment (TIME) of CCAs plays an active role in the pathogenesis and progression of the disease, creating a complex and plastic environment dominated by immune-suppressive populations. Among these, cancer-associated fibroblasts (CAFs) are a key component of the TIME and are associated with worse survival due to their role in maintaining a poorly immunogenic landscape through the deposition of stiff extracellular matrix and release of pro-tumor soluble factors. Improved understanding of CCA tumor biology has driven the development of novel treatments. Combination therapies of cisplatin and gemcitabine with immune checkpoint inhibitors (ICIs) have replaced the decade-long standard doublet chemotherapy, becoming the new standard of care in patients with advanced CCA. However, the survival improvements remain modest prompting research into more effective ways to target the TIME of CCAs. As key mechanisms of immune evasion in CCA are uncovered, novel immune molecules emerge as potential therapeutic targets. Current studies are exploring strategies targeting multiple immune checkpoints, angiogenesis, and tumor-specific antigens that contribute to immune escape. Additionally, the success of ICIs in advanced CCA has led to interest in their application in earlier stages of the disease, such as in adjuvant and neoadjuvant settings. This review offers a comprehensive overview of the immune biology of CCAs and examines how this knowledge has guided clinical drug development, with a focus on both approved and emergent treatment strategies.

DNA vaccines as promising immuno-therapeutics against cancer: a new insight.

Cancer is one of the leading causes of mortality around the world and most of our conventional treatments are not efficient enough to combat this deadly disease. Harnessing the power of the immune system to target cancer cells is one of the most appealing methods for cancer therapy. Nucleotide-based cancer vaccines, especially deoxyribonucleic acid (DNA) cancer vaccines are viable novel cancer treatments that have recently garnered significant attention. DNA cancer vaccines are made of plasmid molecules that encode tumor-associated or tumor-specific antigens (TAAs or TSAs), and possibly some other immunomodulatory adjuvants such as pro-inflammatory interleukins. Following the internalization of plasmids into cells, their genes are expressed and the tumor antigens are loaded on major histocompatibility molecules to be presented to T-cells. After the T-cells have been activated, they will look for tumor antigens and destroy the tumor cells upon encountering them. As with any other treatment, there are pros and cons associated with using these vaccines. They are relatively safe, usually well-tolerated, stable, easily mass-produced, cost-effective, and easily stored and transported. They can induce a systemic immune response effective on both the primary tumor and metastases. The main disadvantage of DNA vaccines is their poor immunogenicity. Several approaches including structural modification, combination therapy with conventional and novel cancer treatments (such as chemotherapy, radiotherapy, and immune checkpoint blockade (ICB)), and the incorporation of adjuvants into the plasmid structure have been studied to enhance the vaccine's immunogenicity and improve the clinical outcome of cancer patients. In this review, we will discuss some of the most promising optimization strategies and examine some of the important trials regarding these vaccines.

Clinical advances of mRNA vaccines for cancer immunotherapy.

The development of mRNA vaccines represents a significant advancement in cancer treatment, with more than 120 clinical trials to date demonstrating their potential across various malignancies, including lung, breast, prostate, melanoma, and more challenging cancers such as pancreatic and brain tumors. These vaccines work by encoding tumor-specific antigens and immune-stimulating molecules, effectively activating the immune system to target and eliminate cancer cells. Despite these promising advancements, significant challenges remain, particularly in achieving efficient delivery and precise regulation of the immune response. This review provides a comprehensive overview of recent clinical progress in mRNA cancer vaccines, discusses the innovative strategies being employed to overcome existing hurdles, and explores future directions, including the integration of CRISPR-Cas9 technology and advancements in mRNA design. Our aim is to provide insights into the ongoing research and clinical trials, highlighting the transformative potential of mRNA vaccines in advancing oncology and improving patient outcomes.

Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers.

Background/Objectives: There is increasing evidence to indicate that histotripsy treatment can enhance the host anti-tumor immune responses both locally at the targeting tumor site as well as systemically from abscopal effects. Histotripsy is a non-invasive ultrasound ablation technology that mechanically disrupts target tissue via cavitation. A key factor contributing to histotripsy-induced abscopal effects is believed to be the release of tumor-specific antigens (TSAs) or tumor-associated antigens (TAAs) that induce a systemic immune response. In this study, we studied the effect of histotripsy treatment on the release of HER2, a well-defined TAA target for cancer immunotherapy. Methods: A range of doses of histotripsy administered to HER2-postive mammary tumor cells in an in vitro cell culture system and an ex vivo tumor were applied. In addition, a single dose of histotripsy was used for an in vivo murine tumor model. The released proteins, and specifically HER2, in both tumor cell-free supernatants and tumor cell pellets were analyzed by a BCA protein assay, an ultra-performance liquid chromatography (UPLC) assay, and Western blot. Results: Our results showed that histotripsy could significantly trigger the release of HER2 proteins in the current study. The level of HER2 proteins was actually higher in tumor cell-free supernatants than in tumor cell pellets, suggesting that HER2 was released from the intracellular domain into the extracellular compartment. Furthermore, proportionally more HER2 protein was released at higher histotripsy doses, indicating free HER2 was histotripsy-dose-dependent. Conclusions: In conclusion, we have qualitatively and quantitatively demonstrated that histotripsy treatment triggers the release of HER2 from the tumor cells into the extracellular compartment. The histotripsy-mediated release of HER2 antigens provides important insights into the mechanism underlying its immunostimulation and suggests the potential of TSA/TAA-based immunotherapies in numerous cancer types.

Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles. We discuss the importance of antigen identification by emphasizing the identification of tumor-specific and tumor-associated antigens and the development of CAR T therapies targeting these antigens. Furthermore, we highlight key structural innovations, including cytokine-armored CARs, protease-regulated CARs, and CARs engineered with chemokine receptors, to enhance tumor infiltration and activity within the immunosuppressive microenvironment. Additionally, novel manufacturing approaches, such as the Sleeping Beauty transposon system, mRNA-based CAR transfection, and in vivo CAR T cell production, are discussed as scalable solution to improve the accessibility of CAR T cell therapies. Finally, we address critical therapeutic limitations, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and suboptimal persistence of CAR T cells. An examination of emerging strategies for countering these limitations reveals that CRISPR-Cas9-mediated genetic modifications and combination therapies utilizing checkpoint inhibitors can improve CAR T cell functionality and durability. By integrating insights from preclinical models, clinical trials, and innovative engineering approaches, this review addresses advances in CAR T cell therapies and their performance in solid tumors.

Advances in Cell and Immune Therapies for Melanoma.

The incidence rate of cutaneous melanoma is on the rise worldwide, due to increased exposure to UV radiation, aging populations, and exposure to teratogen agents. However, diagnosis is more precise, and the increased number of new cases is related to the improved diagnosis tools. Despite better early diagnosis and better therapies, melanoma has remained a significant public health challenge because of its aggressive behavior and high potential for metastasis. In 2020, cutaneous melanoma constituted approximately 1.3% of all cancer deaths that occurred within the European Union, thereby highlighting the necessity for effective prevention, timely diagnosis, and sustainable treatment measures, especially as a growing number of cases occur among younger patients. Melanoma is regarded as one of the most inflamed cancers due to its high immune cell presence and strong response to immunotherapy, fueling the need for development of immune-driven innovative treatments. Approved therapies, including immune checkpoint inhibitors (e.g., anti-PD-1 and anti-CTLA-4), have notably improved survival rates in melanoma. However, the limitations of the PD-1/PD-L1 and CTLA-4 axes inhibitors, such as low response rates, treatment resistance, and toxicity, have driven the need for continued research and advancements in treatment strategies. Current clinical trials are exploring various combinations of immune checkpoint inhibitors with costimulatory receptor agonists, chemotherapy, targeted therapies, and other immunotherapies, with the goal of improving outcomes and reducing side effects for melanoma patients. Emerging approaches, including adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) and oncolytic virotherapy, are showing promise. While CAR-T cell therapy has been less successful in melanoma compared to blood cancers, ongoing research is addressing challenges like the tumor microenvironment and antigen specificity. This review provides an overview of the requirement for advances in these medications, to mark a significant step forward in melanoma management, set to bring a fresh breath of hope for patients.

Comparative Performance of Ante-Mortem Diagnostic Assays for the Identification of Mycobacterium bovis-Infected Domestic Dogs (Canis lupus familiaris).

The domestic dog (Canis lupus familiaris) is a competent host for Mycobacterium (M.) bovis infection but no ante mortem diagnostic tests have been fully validated for this species. The aim of this study was to compare the performance of ante mortem diagnostic tests across samples collected from dogs considered to be at a high or low risk of sub-clinical M. bovis infection. We previously tested a total of 164 dogs at a high risk of infection and here test 42 dogs at a low risk of infection and 77 presumed uninfected dogs with a combination of cell-based and/or serological diagnostic assays previously described for use in non-canid species. The interferon-gamma release assay (IGRA) using peripheral blood mononuclear cells (PBMCs) identified the highest number of test-positive animals (85, 52%), with a suggested specificity of 97.3%, whilst a whole-blood IGRA was found to be unreliable. The production of antigen-specific tumour necrosis factor-alpha (TNF-α) by PBMC in response to a cocktail of ESAT-6 and CFP-10 peptides correlated very strongly with the overall IGRA results, suggesting future diagnostic potential. All three serological assays employed in this study (Idexx M. bovis Ab ELISA, [Idexx Laboratories, Westbrook, ME, USA], DPP VetTB lateral flow assay [Chembio, Medford, NY, USA], and comparative PPD ELISA [in-house]) identified seropositive dogs but, overall, the test-positive rate for the serological assays was only one third that of the cellular-based assays. Circulating serum cytokine concentrations of interferon gamma and TNF-α were not statistically different between the high- and low-risk groups of dogs. While many dogs in the high-risk group had serum biochemical abnormalities, these did not correlate with the findings from the diagnostic TB tests. This study demonstrates, for the first time, the utility of two cellular and three serological assays for detecting sub-clinical M. bovis infections of dogs. Whilst the data suggest a high test specificity for all assays evaluated, further work is needed to validate the sensitivity and specificity of individual or combinations of tests using sufficient numbers of dogs of a known infection status.

Peptide-based CAR-NK cells: A novel strategy for the treatment of solid tumors.

CAR-T cell therapy has been proven to be effective on hematological tumors, although graft-versus-host disease and cytokine release syndrome(CRS) limit its application to a certain extent. However, CAR-T therapy for solid tumors met challenges, among which the lack of tumor-specific antigens (TSA) and immunosuppressive tumor microenvironment (TME) are the most important factors. CAR-NK could be a good alternative to CAR-T in some ways since they can induce mild CRS and are independent of HLA-matching, but the efficacy of CAR-NKs remains limited in solid tumors. CAR cells armed with multiple tumor targeting molecules may obtain higher therapeutic efficacy against solid tumors. Due to large molecular weight, multivalent scFvs cannot be displayed efficiently on T cells and the high affinity of scFv to the target makes it easy to cause on-target, off-tumor(OTOT) toxicity. Peptides with low molecular weight and slightly lower affinity than scFvs allow immune cells to display multiple peptides to increase killing ability and reduce OTOT toxicity. In our study, peptide-based CAR-NK cells were designed to solve the dilemma of CAR-T in solid tumors. Firstly, the peptide-based CAR-NK92MI cells with A1 peptide were constructed and their inhibitory effects on the growth of A549 tumor cells were identified. Secondly, the tri-specific CAR-NK92MI cells with peptides that simultaneously targeted PD-L1, EGFR and VEGFR2 were developed for the combinatory therapy. Tri-specific CAR-NK92MI exhibited comparable killing activities to scFv-based CAR-NK92MI. Moreover, peptide-based CAR NK92MI mitigated OTOT toxicity. Our study implied that peptide-based CAR-NKs could behave as promising tools in solid tumor.

The evolution of cancer immunotherapy: a comprehensive review of its history and current perspectives.

Cancer immunotherapy uses the body's immune system to combat cancer, marking a significant advancement in treatment. This review traces its evolution from the late 19th century to its current status. It began with William Coley's pioneering work using bacterial toxins to stimulate the immune system against cancer cells, establishing the foundational concept of immunotherapy. In the mid-20th century, cytokine therapies like interferons and interleukins emerged, demonstrating that altering the immune response could reduce tumors and highlighting the complex interplay between cancer and the immune system. The discovery of immune checkpoints, regulatory pathways that prevent autoimmunity but are exploited by cancer cells to evade detection, was a pivotal development. Another major breakthrough is CAR-T cell therapy, which involves modifying a patient's T cells to target cancer-specific antigens. This personalized treatment has shown remarkable success in certain blood cancers. Additionally, cancer vaccines aim to trigger immune responses against tumor-specific or associated antigens, and while challenging, ongoing research is improving their efficacy. The historical progression of cancer immunotherapy, from Coley's toxins to modern innovations like checkpoint inhibitors and CAR-T cell therapy, underscores its transformative impact on cancer treatment. As research delves deeper into the immune system's complexities, immunotherapy is poised to become even more crucial in oncology, offering renewed hope to patients globally.

Immunotherapeutic Treatment for Metastatic Prostate Cancer: A Review of Recent Clinical Trials

Metastatic prostate cancer (PC) immunotherapy targets tumor-specific antigens, also known as tumor-associated antigens (TAAs), commonly present in cancer cells. Advancements in PC immunotherapy research studies have shown distinctive and innovative prospective immunotherapy interventions for metastatic PC. Sipuleucel-T, the first immunotherapeutic treatment to treat cases of metastatic castration-resistant PC (mCRPC), is one of these notable, unique, and innovative immunotherapies. This review examines the types of immunotherapies for metastatic PC, along with immunotherapy and combination treatments with immunotherapy, with a particular emphasis on immunotherapy in clinical trials. The goal of immunotherapeutic treatments is to restore the host immune system’s ability to combat PC cells, primarily through natural mechanisms (e.g., the action of cytotoxic T cells on cancer cells) and a variety of mechanisms of action that elicit the desired effect through targeting TAAs, ligand binding, and immune checkpoint inhibitors (ICIs). Researchers have also linked multiple gene mutations and expressions to metastatic PC susceptibility, such as CDK12 mutations. The ability of immunomodulators to enhance the immunoreactivity of PC patients has suggested their use in combination therapeutic approaches with immunotherapy for PC treatment. Recent immunotherapy treatments for metastatic PC have focused on exploring different immune system checkpoint inhibitors, genetic alterations, and PC biomarkers to improve the clinical progression of metastatic PC patients, their overall survival rate, and the partial or complete remission of cancer cells. Furthermore, ongoing clinical research studies on immunotherapy treatment for metastatic PC are currently investigating not only monotherapy immunotherapy treatments but also various combination therapies that can enhance the immunotherapy treatment’s effectiveness.

Emerging strategies in cancer immunotherapy: Expanding horizons and future perspectives

Cancer immunotherapy has revolutionized oncology by harnessing the body’s immune system to target and eradicate malignant cells. This review delves into emerging strategies in cancer immunotherapy, focusing on novel approaches and future directions of this rapidly evolving field. Key areas of exploration include immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, and cancer vaccines. ICIs, which target proteins such as cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/programmed cell death ligand 1, have shown significant efficacy in various cancers, transforming clinical outcomes. CAR-T cell therapy, with its ability to genetically modify T-cells to attack cancer cells, has demonstrated remarkable success in hematologic malignancies and is being adapted for solid tumors. Cancer vaccines designed to stimulate an immune response against specific tumor antigens are also advancing with promising clinical results. Despite these advances, challenges such as immunogenicity, side effects, and treatment resistance remain. This review provides a comprehensive overview of the latest developments, clinical trials, and future perspectives in cancer immunotherapy, highlighting the potential for these strategies to redefine cancer treatment.

Potent prophylactic cancer vaccines harnessing surface antigens shared by tumour cells and induced pluripotent stem cells.

The development of prophylactic cancer vaccines typically involves the selection of combinations of tumour-associated antigens, tumour-specific antigens and neoantigens. Here we show that membranes from induced pluripotent stem cells can serve as a tumour-antigen pool, and that a nanoparticle vaccine consisting of self-assembled commercial adjuvants wrapped by such membranes robustly stimulated innate immunity, evaded antigen-specific tolerance and activated B-cell and T-cell responses, which were mediated by epitopes from the abundant number of antigens shared between the membranes of tumour cells and pluripotent stem cells. In mice, the vaccine elicited systemic antitumour memory T-cell and B-cell responses as well as tumour-specific immune responses after a tumour challenge, and inhibited the progression of melanoma, colon cancer, breast cancer and post-operative lung metastases. Harnessing antigens shared by pluripotent stem cell membranes and tumour membranes may facilitate the development of universal cancer vaccines.

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

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.