Screening Neoantigen Peptides for Personalized Colorectal Cancer Vaccines Using MHC Affinity

Neoantigens with MHC molecular affinity variation of 1-4 and HLA Type 1 association showed the highest immunogenicity, activating CD4+/CD8+ T cells and NK cells with 96.6% dendritic cell maturation versus 0.051% in controls.

Whole exome sequencing of patient-derived colon cancer cells. In silico 9-amino-acid neoantigen prediction. In vitro dendritic cell-mediated antigen presentation to T cells. Immune response assessed by flow cytometry and ELISpot. MHC affinity variation and HLA typing correlated with immunogenicity.

Personalized cancer vaccines are one of the most promising cancer immunotherapy approaches, but identifying the right peptides is a bottleneck. This MHC affinity screening method could make neoantigen vaccine development faster and more reliable, bringing personalized cancer treatment closer to routine clinical use.

Cancer vaccines using neoantigen peptides are in clinical trials at major cancer centers. The biggest challenge is efficient screening — most patients's tumors have hundreds of mutations, but only a few produce peptides that trigger strong immune responses. This MHC affinity-based screening approach could become a standard tool for selecting the most effective vaccine targets.

In vitro study — immune responses in a dish may not predict clinical vaccine efficacy. Patient-derived cells from a limited number of cases. The 14-day in vitro T cell expansion may not reflect in vivo kinetics. Manufacturing individual neoantigen vaccines remains complex and expensive.