MHC I on the surface of tumor cells is capable of presenting highly specific peptides called neoantigens. Since they are not expressed in normal cells, these peptides are ideal targets for tumor immunotherapy and tumor vaccines. In recent years, immunotherapy based on tumor neoantigens has received significant attention, but the accurate identification of tumor-specific neoantigens from the cell membrane surface remains a difficult challenge. Traditional methods for tumor neoantigen identification use genomic or transcriptomic sequencing techniques to identify tumor-specific mutations (mostly point mutations) from DNA or mRNA, and then generate candidate peptides that have the potential to become tumor-specific neoantigens by software prediction only.
Confirmation of Neoantigen Services
Once the list of candidate neoantigens is available, Alfa Oncology’ selection of the effector T cell population that will undergo the screening assay is a key determinant of neoantigen identification. In theory, tissues or fluids from which T cells can be isolated and expanded are potential sources for neoantigen immunogenicity screening. Such as TILs, PBMC, pre-enriched T cell population, etc.
T cells accumulate at tumor sites, possibly due to local antigen-specific clonal expansion. The results of intratumoral TCR deep sequencing also showed that the tumor-infiltrating T cell receptor repertoire is generally more oligoclonal. Therefore, TILs are a preferred source of T cells to detect T cells that recognize neoantigens. Although the most attractive source in terms of T cell composition, TILs have not been expanded with high success rates, and even when expanded from contiguous tumor fragments, TILs can be highly heterogeneous. One of the major challenges in identifying neoantigens is finding non-invasive sources of T cells for immune screening. PBMCs from blood extractions represent the most attractive source for this purpose. Given the low frequency of neoantigen-specific T cells, enrichment methods rely on the selection of specific T cell populations and their expansion in vitro to obtain cell quantities for immunogenicity screening.