Antigen discovery for the development of cancer immunotherapy

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.

Automated summary

Effective T cell antitumor immunity is essential for successful cancer immunotherapy. Mass spectrometry-based survey of tumor antigens (immunopeptidomics) combined with other omics platforms has contributed to the identification and quantification of T cell antigens. This review discusses the types of tumor antigens for targeted cancer immunotherapy and the importance of immunopeptidomics methods in MHC peptide identification. It also highlights the integration of mass spectrometry-driven approaches with other technologies in the discovery of targetable T cell antigens for cancer immunotherapy.