Whole-Exome Sequencing to Screen Personal Neoantigens With High Immunogenicity in Patients With Microsatellite Stability (MSS)-Advanced Colorectal Cancer.

Abstract

To develop a personalized neoantigen therapy strategy for microsatellite stability (MSS)-advanced colorectal cancer (CRC), neoantigens from collected human CRC samples were screened, and the feasibility and effectiveness of these neoantigens in treating CRC were explored. Whole-exome sequencing and transcriptome sequencing were performed to identify somatic mutations, RNA expression, and human leukocyte antigen alleles. Based on these data, neoantigen candidates were predicted, and their immunogenicity was evaluated. Selected neoantigens from patients elicited enhanced T-cell responses in CRC peripheral blood lymphocytes. Mutated peptides SOX9-V144M, ZNF169-A275S, CDH4-V456M, NIM1K-T66M, and MAP3K9-R1008Q were more effective than nonmutated ones in Patient 1. Vaccination with mutant peptides ZNF169-A275S and CDH4-V456M inhibited tumor growth in an autologous humanized CRC mouse model. Highly immunogenic neoantigens are strong candidates for personalized cancer therapy, showing promise for translating into effective treatments for CRC patients with advanced disease.