Neoantigens and their clinical applications in human gastrointestinal cancers

Abstract

Background: Tumor-specific neoantigens are ideal targets for cancer immunotherapy. As research findings have proved, neoantigen-specific T cell activity is immunotherapy's most important determinant.

Main text: There is sufficient evidence showing the role of neoantigens in clinically successful immunotherapy, providing a justification for targeting. Because of the significance of the pre-existing anti-tumor immune response for the immune checkpoint inhibitor, it is believed that personalized neoantigen-based therapy may be an imperative approach for cancer therapy. Thus, intensive attention is given to strategies targeting neoantigens for the significant impact with other immunotherapies, such as the immune checkpoint inhibitor. Today, several algorithms are designed and optimized based on Next-Generation Sequencing and public databases, including dbPepNeo, TANTIGEN 2.0, Cancer Antigenic Peptide Database, NEPdb, and CEDAR databases for predicting neoantigens in silico that stimulates the development of T cell therapies, cancer vaccine, and other ongoing immunotherapy approaches.

Conclusions: In this review, we deliberated the current developments in understanding and recognition of the immunogenicity of newly found gastrointestinal neoantigens as well as their functions in immunotherapies and cancer detection. We also described how neoantigens are being developed and how they might be used in the treatment of GI malignancies.

Keywords: CAR-T cell; Gastrointestinal cancers; Immunotherapy; Neoantigen; Tumor.

Fig. 1

The typical recognition of tumor neoantigens by immune cells. The tumor-specific neoantigens derived from genetic alterations such as mutated DNA or altered ORF are presented by APCs and recognized as foreign molecules by the adaptive immune cells

Fig. 2

Development of a personalized approach for targeting GI neoantigens by CAR-T cell-based vaccine. A personalized approach for targeting GI neoantigens might be impressive due to foremost advances in genetic engineering for expansion of autologous T cells and development of neoantigen specific-CAR-T cells (as vaccines encoding marked neoantigens). The specific approaches as combined with other therapies such as immune checkpoint inhibitors and anti PD-1 and CTLA-4 may be more effective for elimination of GI tumors