Neoantigen vaccine and neoantigen‐specific cell adoptive transfer therapy in solid tumors: Challenges and future directions. Issue 2 (30th August 2022)

• Record Type: Journal Article
• Authors: Shen, Yanwei; Yu, Lu; Xu, Xiaoli; Yu, Shaojun; Yu, Zhuo
• Is Part Of: Cancer innovation. Volume 1:Issue 2(2022)
• Page Start: 168
• Page End: 182
• Publication Date: 2022-08-30
• Subjects: neoantigen -- cancer vaccine -- immunotherapy -- tumor microenvironment -- heterogeneity -- precision medicine; Cancer -- Research -- Periodicals; Oncology -- Periodicals; Cancer -- Treatment -- Technological innovations; Cancer -- Diagnosis -- Technological innovations; Cancer -- Research; Cancer -- Treatment -- Technological innovations; Oncology; Periodicals; 616.994
• DOI: 10.1002/cai2.26
• Languages: English
• ISSNs: 2770-9183

Abstract

Abstract: The phenomenon of tumor hierarchy and genetic instability can be explained by the "two‐hits theory" and results in the occurrence of many somatic mutations. The expression of nonsynonymous mutations results in the production of mutant proteins from tumor cells, namely tumor‐specific antigens called neoantigens. Because neoantigens do not exist in healthy cells, they have the potential to stimulate antitumor immune responses by CD4+ and CD8+ T‐cell activation without jeopardizing normal tissues. Immunotherapy has reshaped the cancer treatment paradigm in recent decades with the introduction of immune‐checkpoint blockade therapy and transgenic T‐cell receptor/chimeric antigen receptor T cells. However, these strategies performed poorly in solid tumors because of the obstacles of the immunosuppressive microenvironment caused by regulatory T cells and other suppressor cells. Therefore, other immunotherapeutic strategies are under development, such as personalized vaccines, to trigger de novo T‐cell responses against neoantigens and lead to the amplification of tumor‐specific T‐cell subclones. Neoantigen epitope prediction algorithms have enabled the detection of neoantigens and the creation of tailored neoantigen vaccines as a result of the fast development of next‐generation sequencing and cancer bioinformatics. Here we provide an overview of the current neoantigen cancer vaccines and adoptive T‐cell transfer therapy with neoantigen‐specific lymphocytes. We also discuss the challenges in developing neoantigen‐targeted immunotherapeutic strategies for cancer. Abstract : Recent technological advances of next‐generation sequencing and bioinformatics have made it possible to discover more abundant and specific neoantigens encoded by tumor‐specific somatic mutations. Precise cancer medicine of therapeutic vaccines designed from personalized neoantigens have been proven effective and safe in patients with melanoma, non‐small cell lung cancer, and head and neck squamous carcinoma, and so forth. Discoveries of the phenotypes, functionality, and long‐lasting memory potential of tumor‐infiltrating lymphocytes trigger deeper evaluation of cancer vaccine study and vaccine‐induced neoantigen‐specific CD4+ and CD8+ T‐cell adoptive transfer therapy, which is warranted to improve immunotherapeutic activity and optimize vaccination strategies.