Abstract
BACKGROUND: Knowledge about and identification of T cell tumor antigens may inform the development of T cell receptor-engineered adoptive cell transfer or personalized cancer vaccine immunotherapy. Here, we review antigen processing and presentation and discuss limitations in tumor antigen prediction approaches. METHODS: Original articles covering antigen processing and presentation, epitope discovery, and in silico T cell epitope prediction were reviewed. RESULTS: Natural processing and presentation of antigens is a complex process that involves proteasomal proteolysis of parental proteins, transportation of digested peptides into the endoplasmic reticulum, loading of peptides onto major histocompatibility complex (MHC) class I molecules, and shuttling of peptide:MHC complexes to the cell surface. A number of T cell tumor antigens have been experimentally validated in patients with cancer. Assessment of predicted MHC class I binding and total score for these validated T cell antigens demonstrated a wide range of values, with nearly one-third of validated antigens carrying an IC50 of greater than 500 nM. CONCLUSIONS: Antigen processing and presentation is a complex, multistep process. In silico epitope prediction techniques can be a useful tool, but comprehensive experimental testing and validation on a patient-by-patient basis may be required to reliably identify T cell tumor antigens.
Original language | English (US) |
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Journal | Journal for immunotherapy of cancer |
Volume | 8 |
Issue number | 2 |
DOIs | |
State | Published - Aug 1 2020 |
Keywords
- T-lymphocytes
- antigen presentation
- antigens
- immunotherapy
- neoplasm
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research