Chasing neoantigens; invite naïve T cells to the party

Curr Opin Immunol. 2022 Apr;75:102172. doi: 10.1016/j.coi.2022.102172. Epub 2022 Mar 10.

Abstract

Neoantigens are commonly defined as HLA-bound peptides that are altered as a consequence of DNA damage and recognized by T cells. Current efforts to target neoantigens in therapy rely on algorithms that predict HLA-binding and immunogenicity from DNA sequence data. Datasets obtained by mass spectrometry of peptides eluted from mono-allelic cell lines have greatly improved our ability to predict HLA-binding. The main challenge lies in selecting those that are likely to be immunogenic. Here we argue that the current approach of searching for antigens that have evoked T-cell responses in untreated patients may underestimate immunogenicity. Results from clinical trials show that cancer vaccines often primarily engage the naïve T-cell repertoire. We therefore propose a new pipeline where HLA-binding is detected directly by mass spectrometry and immunogenicity is determined as the ability to prime naïve T cells from healthy donors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm*
  • Cancer Vaccines*
  • Humans
  • Peptides
  • T-Lymphocytes

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Peptides