A proteogenomic approach to target neoantigens in solid tumors

Expert Rev Proteomics. 2020 Nov-Dec;17(11-12):797-812. doi: 10.1080/14789450.2020.1881889.

Abstract

Introduction: Proteogenomic techniques find applications in identifying novel cancer-specific peptides called neoantigens; they are non-self peptides derived from tumor-specific non-synonymous mutations. These peptides with MHCs are recognized by the T cells and induce an antitumor response. Due to their selective expression of tumor cells, neoantigens are considered attractive targets for cancer immunotherapy.

Areas covered: In this review, we have discussed the proteogenomic strategies to identify neoantigens. We have also provided a neoantigen identification pipeline using data from whole-exome sequencing, RNA sequencing, and MHC peptidomics. Further, we have reviewed recent tools for neoantigen discovery.

Expert commentary: The limitations in instrument sensitivity and availability of bioinformatics tools have restricted the identification of neoantigens from tumor samples. Nonetheless, the recent improvement in genome sequencing, mass spectrometry technologies, and the development of reliable algorithms for epitope prediction provide hope for efficient identification of neoantigens. Translating this workflow on patient samples would represent a massive advancement in neoantigen identification methods, leading to the constitution of novel personalized neoantigen cancer vaccines.

Keywords: Cancer immunotherapy; neoantigens; proteogenomics.

Publication types

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

MeSH terms

  • Antigens, Neoplasm*
  • Humans
  • Immunotherapy*
  • Mass Spectrometry
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Proteogenomics*
  • T-Lymphocytes

Substances

  • Antigens, Neoplasm