Personalized immunotherapy in colorectal cancer

Abstract

The fields of cancer immunology and immunotherapy have made dramatic progress in the past 20 years. Various approaches to cancer immunotherapies, including cancer vaccines using peptides, proteins, DNA, and dendritic cells, have been developed to activate antigen-specific immune cells and their efficacy has been clinically examined. Herein, we summarize previously performed clinical trials of various immunotherapies against colorectal cancer (CRC), including our own novel immunotherapeutic approach, the "personalized peptide vaccine", in which human leukocyte antigen (HLA)-matched vaccine peptides are selected based on pre-existing host immunity before vaccination. In the near future, neoepitopes identified through massive DNA sequencing of the genetic alterations in tumor cells, combined with robust T cell epitope predictions in each patient might be targeted as a personalized immunotherapy for CRC. ARTICLE HISTORY

Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

“…Tumor-derived neoantigens that have not been able to stimulate the immune responses cannot induce strong immune responses in the vaccine formulation ( 180 , 181 ). Therefore, after selecting the ideal neoantigens and matching them with the patient MHC, it is necessary to evaluate the pre-existing immune responses against those neoantigens by determining the frequency of antigen-specific cytotoxic T cells (CTLs) as well as the antigen-specific IgG titer in the serum ( 15 , 182 ). Considering the pre-existing immunity in neoantigens selection could enhance the vaccination efficacy and reduce the adverse events ( 15 ).…”

“…Considering the pre-existing immunity in neoantigens selection could enhance the vaccination efficacy and reduce the adverse events ( 15 ). Clinical trials using this type of personalized vaccination have shown encouraging results in inducing an antitumor immune response and increasing OS even in chemoresistant CRC patients ( 178 , 179 , 182 ). The process of personalized immunotherapy in CRC is illustrated in Figure 1 .…”