Neoantigen vaccine and neoantigen-specific cell adoptive transfer therapy in solid tumors: Challenges and future directions.

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.