Neoantigens exhibit high immunogenic potential and confer a uniqueness to tumor cells, making them ideal targets for personalized cancer immunotherapy. Neoantigens originate from tumor-specific genetic alterations, abnormal viral infections, or other biological mechanisms, including atypical RNA splicing events and post-translational modifications (PTMs). These neoantigens are recognized as foreign by the immune system, eliciting an immune response that largely bypasses conventional mechanisms of central and peripheral tolerance. Advances in next-generation sequencing (NGS), mass spectrometry (MS), and artificial intelligence (AI) have greatly expedited the rapid detection and forecasting of neoantigens, markedly propelling the development of diverse immunotherapeutic strategies, including cancer vaccines, adoptive cell therapy, and antibody treatment. In this review, we comprehensively explore the discovery and characterization of neoantigens and their clinical use within promising immunotherapeutic frameworks. Additionally, we address the current landscape of neoantigen research, the intrinsic challenges of the field, and potential pathways for clinical application in cancer treatment.
Humans ; Neoplasms/therapy* ; Precision Medicine/methods* ; Immunotherapy/methods* ; Antigens, Neoplasm/genetics* ; Cancer Vaccines/immunology* ; High-Throughput Nucleotide Sequencing

Tumor immunotherapy has revolutionized the treatment prospects for various malignant tumors. Immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T) , as representative of tumor immunotherapy, have achieved tremendous success in clinical practice and have become the first-line clinical treatment options for certain tumors. This article summarizes the progress and challenges of immune checkpoint inhibitors and CAR-T therapy in tumor treatment, and discusses the future direction of tumor therapeutic vaccines development. Identifying novel therapeutic targets within the realm of tumor immunology, engineering innovative drug delivery systems, and employing combinatorial therapeutic strategies are poised to enhance therapeutic efficacy and patient outcomes in oncology, thereby extending benefits to a broader patient population.
Humans ; Neoplasms/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy/methods* ; Immunotherapy, Adoptive/methods* ; Animals ; Cancer Vaccines/therapeutic use*

Objective To characterize the properties of Hepa1-6-derived microparticles (Hepa1-6-MPs), investigate their stimulatory effects on dendritic cells (DCs) and their cellular uptake pathways, and explore the specific cytotoxic effects of CD8⁺ T cells induced by Hepa1-6-MP-loaded DCs on hepatoma cell lines, with the aim of developing a novel immunotherapeutic model for hepatocellular carcinoma (HCC). Methods The isolated Hepa1-6-MPs were identified using Western blotting, transmission electron microscopy (TEM) and dynamic light scattering (DLS). Flow cytometry was used to assess the uptake pathways of Hepa1-6-MPs by DCs. Subsequently, enzyme-linked immunosorbent assay (ELISA) was used to measure the effects of Hepa1-6-MP-loaded DCs on the release levels of tumor necrosis factor α(TNF-α) and interferon γ(IFN-γ) into the supernatant of CD8⁺ T cells. Lactate dehydrogenase (LDH) tests were conducted to evaluate the cytotoxic effects of CD8⁺ T cells stimulated by Hepa1-6-MP-loaded DCs on hepatoma cells. Results The morphology, size and protein markers of Hepa1-6-MPs met the established criteria. Hepa1-6-MPs enhanced the expression of DC maturation markers CD80 and CD86, and were internalized by DCs via clathrin-mediated endocytosis and phagocytosis pathways. Subsequently, Hepa1-6-MP-loaded DCs stimulated CD8⁺ T cells to release high levels of TNF-α and IFN-γ, which induced their specific cytotoxicity against HCC cells. Conclusion These findings suggest that Hepa1-6-MP-loaded DCs may be a promising HCC immunotherapeutic tool.
Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Dendritic Cells/immunology* ; Humans ; Cancer Vaccines/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Interferon-gamma/immunology* ; Cell-Derived Microparticles/immunology* ; Animals

Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy. The oncolytic influenza A virus, although promising in preclinical investigations, remains to be implemented in clinical practice. Recent progress in genetic engineering, coupled with experiential insights, offers opportunities to enhance the therapeutic efficacy of the influenza A virus. This review explores the use of the influenza virus, its attenuated forms, and associated vaccines in cancer immunotherapy, highlighting their respective advantages and challenges. We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors, aiming to maximize their clinical impact. Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.
Humans ; Neoplasms/immunology* ; Immunotherapy/trends* ; Influenza A virus/immunology* ; Oncolytic Virotherapy/trends* ; Animals ; Cancer Vaccines/therapeutic use* ; Oncolytic Viruses ; Genetic Engineering ; Immune Checkpoint Inhibitors/therapeutic use*

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

Cancer remains a major global health challenge, with conventional treatments like chemotherapy and radiotherapy often hindered by significant side effects, lack of specificity, and limited efficacy in advanced cases. Among emerging therapeutic strategies, mRNA vaccines have shown remarkable potential due to their adaptability, rapid production, and capability for personalized cancer treatment. This review provides an in-depth analysis of messenger RNA (mRNA) vaccines as a therapeutic approach for cancer immunotherapy, focusing on their molecular biology, classification, mechanisms, and clinical studies. Derived from reported literature and data on clinicaltrials.gov, it examines studies on mRNA vaccines encoding tumor-specific antigens (TSAs), tumor-associated antigens (TAAs), immunomodulators, and chimeric antigen receptors (CARs) across various cancer types. The review highlights the ability of mRNA vaccines to encode TSAs and TAAs, enabling personalized cancer treatments, and classifies these vaccines into non-replicating and self-amplifying types. It further explores their mechanisms of action, including antigen presentation and immune activation, while emphasizing findings from clinical studies that demonstrate the potential of mRNA vaccines in cancer therapy. Despite their promise, challenges remain in enhancing delivery systems, improving immunogenicity, and addressing tumor heterogeneity. Overcoming these obstacles will require further investigation to fully harness the potential of mRNA vaccines in personalized cancer treatment.
Humans ; Cancer Vaccines/immunology* ; Neoplasms/immunology* ; mRNA Vaccines/therapeutic use* ; Immunotherapy/methods* ; Antigens, Neoplasm/genetics* ; RNA, Messenger/therapeutic use*

Objective: To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC). Methods: DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 Results: We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders. Conclusion In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.
Adult ; Aged ; Cancer Vaccines/therapeutic use* ; China ; Dendritic Cells/immunology* ; Female ; Humans ; Immunotherapy/methods* ; Injections, Intradermal ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/therapy* ; Nasopharyngeal Neoplasms/therapy* ; T-Lymphocytes, Cytotoxic/immunology* ; Viral Matrix Proteins/therapeutic use* ; Young Adult

Cancer is the leading cause of death worldwide. In developed as well as developing countries, breast cancer is the most common cancer found among women. Currently, treatment of breast cancer consists mainly of surgery, chemotherapy, hormone therapy, and radiotherapy. In recent years, because of increased understanding of the therapeutic potential of immunotherapy in cancer prevention, cancer vaccines have gained importance. Here, we review various immunotherapeutic breast cancer vaccines including peptide-based vaccines, whole tumor cell vaccines, gene-based vaccines, and dendritic cell vaccines. We also discuss novel nanotechnology-based approaches to improving breast cancer vaccine efficiency.
Allergy and Immunology ; Breast Neoplasms* ; Breast* ; Cancer Vaccines ; Cause of Death ; Dendritic Cells ; Developing Countries ; Drug Therapy ; Female ; Humans ; Immunotherapy ; Radiotherapy ; Vaccines*

Listeria monocytogenes (L. monocytogenes, LM) is an excellent tumor vaccine vector. In this study, recombinant LM vaccine candidate expressing human papillomavirus type 16 (HPV16) E7 protein was constructed and its charactericts were determined. Through homologous recombination, E7 gene was cloned in frame with the LM4 Phly promoter-signal sequence, and introduced into the chromosome of LM4. The recombinant strain named LM4△hly::E7 with the plasmid-free and antibiotic-resistant gene-free was constructed. LM4△hly::E7 could express and secrete E7-LLO fusion protein; its size is 66 kDa and has immunological activity. Furthermore, LM4△hly::E7 could multiply in RAW264.7 macrophages by confocal laser scanning microscope. Additionally, LM4△hly::E7 could induce specific antibodies against E7 in immunized mice in ELISA. Also, the 50% lethal dose (LD₅₀) of LM4△hly::E7 strain was 3.863×10⁹ CFU (Colony-Forming Units) in C57BL/6 mice with intraperitoneal immunization, which was more attenuated than wild type LM4. Mice immunized with LM4△hly::E7 did not show obvious pathological change. These data show that LM4△hly::E7 expressing E7-LLO fusion protein has good safety, which may provide the materials for research of antitumor effect and would be a promising vaccine candidate for cervical cancer.
Animals ; Cancer Vaccines ; immunology ; Listeria monocytogenes ; Mice ; Mice, Inbred C57BL ; Papillomavirus E7 Proteins ; immunology ; Papillomavirus Infections ; prevention & control ; Plasmids ; RAW 264.7 Cells ; Recombinant Fusion Proteins ; immunology ; Vaccines, Attenuated ; immunology ; Viral Vaccines ; immunology

OBJECTIVETo investigate the humoral and cellular immune responses induced by MUC1-2VNTR DNA vaccine in multiple myeloma (MM) tumor-bearing mice.

METHODSIn vitro, multiple myeloma cells were transfected by plasmid pcDNA3.1-2VNTR/myc-hisB with Lipofectamine2000. The above-mentioned mouse myeloma cells were inoculated subcutaneously into female BALB/c mice for establishing tumor-bearing animal models. These female BALB/c mice were immunized with pcDNA-2VNTR/myc-hisB or pcDNA/myc-hisB. The cytotoxic T lymphocyte (CTL) activity was detected by the LDH method and the spleen lymphocyte proliferation activity was detected by CCK-8 method.

RESULTSAfter immunization of BALB/c tumor-bearing mice with recombinant plasmid for 25 days, the tumor mass (0.5605 ± 0.2065 g) was significantly lighter than that in the empty plasmid control group (1.521 ± 0.6985 g) (P < 0.01) and the control group (1.5315 ± 0.5425 g) (P < 0.01). The difference of tumor mass was not statislically significant between empty plasmid control group (1.521 ± 0.6985 g) and the control group (1.5315 ± 0.5425 g) (P > 0.05). The CTL and NK cell activity was significantly higher in the group of intramuscular injection with recombinant plasmid than that in control group. The spleen lymphocyte proliferation was statistically significantly increased after being immunized with recombinant plasmid pcDNA3.1-2VNTR/myc-hisB, compared with empty vector (P < 0.01). The results showed that MUC1-2VNTR gene immunization could induce anti-tumor effect in MM tumor-bearing mice.

CONCLUSIONMUC1-2VNTR DNA immunization can elicit both humoral and cellular tumor specific immune response to multiple myeloma in MM tumor-bearing mice. It suggested that the MUC1-2VNTR DNA vaccine may be a potential treatment measure for patients with MM.

Animals ; Cancer Vaccines ; therapeutic use ; Female ; Genetic Vectors ; Humans ; Immunization ; Killer Cells, Natural ; immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Minisatellite Repeats ; Mucin-2 ; genetics ; Multiple Myeloma ; immunology ; therapy ; Neoplasm Transplantation ; Plasmids ; Spleen ; cytology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Vaccines, DNA ; therapeutic use