Antigen discovery for the development of cancer immunotherapy

Abstract

Central to successful cancer immunotherapy is effective T cell antitumor immunity. Multiple targeted immunotherapies engineered to invigorate T cell-driven antitumor immunity rely on identifying the repertoire of T cell antigens expressed on the tumor cell surface. Mass spectrometry-based survey of such antigens ("immunopeptidomics") combined with other omics platforms and computational algorithms has been instrumental in identifying and quantifying tumor-derived T cell antigens. In this review, we discuss the types of tumor antigens that have emerged for targeted cancer immunotherapy and the immunopeptidomics methods that are central in MHC peptide identification and quantification. We provide an overview of the strength and limitations of mass spectrometry-driven approaches and how they have been integrated with other technologies to discover targetable T cell antigens for cancer immunotherapy. We highlight some of the emerging cancer immunotherapies that successfully capitalized on immunopeptidomics, their challenges, and mass spectrometry-based strategies that can support their development.

Keywords: Cancer immunotherapy; Immunopeptidomics; Mass spectrometry; Neoantigens; Tumor-associated antigens; Tumor-specific antigens.