Early efforts to identify tumor-associated antigens over the last decade have provided unique cancer epitopes for targeted cancer therapy. MAGE-A proteins are a subclass of cancer/testis (CT) antigens that are presented on the cell surface by MHC class I molecules as an immune-privileged site. This is due to their restricted expression to germline cells and a wide range of cancers, where they are associated with resistance to chemotherapy, metastasis, and cancer cells with an increasing potential for survival. This makes them an appealing candidate target for designing an effective and specific immunotherapy, thereby suggesting that targeting oncogenic MAGE-As with cancer vaccination, adoptive T-cell transfer, or a combination of therapies would be promising. In this review, we summarize and discuss previous and ongoing (pre-)clinical studies that target these antigens, while bearing in mind the benefits and drawbacks of various therapeutic strategies, in order to speculate on future directions for MAGE-A-specific immunotherapies.

Disialoganglioside GD2 is a promising target for immunotherapy with expression primarily restricted to neuroectodermal and epithelial tumor cells. Although its role in the maintenance and repair of neural tissue is well-established, its functions during normal organism development remain understudied. Meanwhile, studies have shown that GD2 plays an important role in tumorigenesis. Its functions include proliferation, invasion, motility, and metastasis, and its high expression and ability to transform the tumor microenvironment may be associated with a malignant phenotype. Structurally, GD2 is a glycosphingolipid that is stably expressed on the surface of tumor cells, making it a suitable candidate for targeting by antibodies or chimeric antigen receptors. Based on mouse monoclonal antibodies, chimeric and humanized antibodies and their combinations with cytokines, toxins, drugs, radionuclides, nanoparticles as well as chimeric antigen receptor have been developed. Furthermore, vaccines and photoimmunotherapy are being used to treat GD2-positive tumors, and GD2 aptamers can be used for targeting. In the field of cell therapy, allogeneic immunocompetent cells are also being utilized to enhance GD2 therapy. Efforts are currently being made to optimize the chimeric antigen receptor by modifying its design or by transducing not only αβ T cells, but also γδ T cells, NK cells, NKT cells, and macrophages. In addition, immunotherapy can combine both diagnostic and therapeutic methods, allowing for early detection of disease and minimal residual disease. This review discusses each immunotherapy method and strategy, its advantages and disadvantages, and highlights future directions for GD2 therapy.

Autoimmune diseases result from imbalances in the immune system and disturbances in the mechanisms of immune tolerance. T-regulatory cells (Treg) are key factors in the formation of immune tolerance. Tregs modulate immune responses and repair processes, controlling the innate and adaptive immune system. The use of Tregs in the treatment of autoimmune diseases began with the manipulation of endogenous Tregs using immunomodulatory drugs. Then, a method of adoptive transfer of Tregs grown in vitro was developed. Adoptive transfer of Tregs includes polyclonal Tregs with non-specific effects and antigen-specific Tregs in the form of CAR-Treg and TCR-Treg. This review discusses non-specific and antigen-specific approaches to the use of Tregs, their advantages, disadvantages, gaps in development, and future prospects.

In immunology, the discovery of regulatory T (Treg) cells was a major breakthrough. Treg cells play a key role in pregnancy maintenance, in the prevention of autoimmune responses, and in the control of all immune responses, including responses to self cells, cancer, infection, and a transplant. It is currently unclear whether Treg cells are capable of long-term memory of an encounter with an antigen. Although the term “immunological memory” usually means an enhanced ability to protect the body from reinfection, the memory of the suppressive activity of Treg cells helps to avoid the state of generalized immunosuppression that may result from the second activation of the immune system. In this review, we would like to discuss the concept of regulatory memory and in which tissues memory Treg cells can perform their functions.

IL‐18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL‐18 production are found in the gene promoter region. We investigated the association of SNPs in the IL‐18 promoter at −607 and −137 with the level of IL‐18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL‐18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS‐stimulated IL‐18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL‐18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL‐18 gene influence the level of IL‐18 protein production by PBMC from healthy donors in Southwestern Siberia.

Significant strides have been made in identifying tumour‐associated antigens over the past decade, revealing unique epitopes crucial for targeted cancer therapy. Among these, the New York esophageal squamous cell carcinoma (NY‐ESO‐1) protein, a cancer/testis antigen, stands out. This protein is presented on the cell surface by major histocompatibility complex class I molecules and exhibits restricted expression in germline cells and various cancers, marking it as an immune‐privileged site. Remarkably, NY‐ESO‐1 serves a dual role as both a tumour‐associated antigen and its own adjuvant, implying a potential function as a damage‐associated molecular pattern. It elicits strong humoural immune responses, with specific antibody frequencies significantly correlating with disease progression. These characteristics make NY‐ESO‐1 an appealing candidate for developing effective and specific immunotherapy, particularly for advanced stages of disease. In this review, we provide a comprehensive overview of NY‐ESO‐1 as an immunogenic tumour antigen. We then explore the diverse strategies for targeting NY‐ESO‐1, including cancer vaccination with peptides, proteins, DNA, mRNA, bacterial vectors, viral vectors, dendritic cells and artificial adjuvant vector cells, while considering the benefits and drawbacks of each strategy. Additionally, we offer an in‐depth analysis of adoptive T‐cell therapies, highlighting innovative techniques such as next‐generation NY‐ESO‐1 T‐cell products and the integration with lymph node‐targeted vaccines to address challenges and enhance therapeutic efficacy. Overall, this comprehensive review sheds light on the evolving landscape of NY‐ESO‐1 targeting and its potential implications for cancer treatment, opening avenues for future tailored directions in NY‐ESO‐1‐specific immunotherapy.Highlights: Endogenous immune response: NY‐ESO‐1 exhibited high immunogenicity, activating endogenous dendritic cells, T cells and B cells. NY‐ESO‐1‐based cancer vaccines: NY‐ESO‐1 vaccines using protein/peptide, RNA/DNA, microbial vectors and artificial adjuvant vector cells have shown promise in enhancing immune responses against tumours. NY‐ESO‐1‐specific T‐cell receptor‐engineered cells: NY‐ESO‐1‐targeted T cells, along with ongoing innovations in engineered natural killer cells and other cell therapies, have improved the efficacy of immunotherapy.