Level of neo-epitope predecessor and mutation type determine T cell activation of MHC binding peptides.

Journal: Journal for immunotherapy of cancer
PMID: 31118084

Abstract

BACKGROUND: Targeting epitopes derived from neo-antigens (or "neo-epitopes") represents a promising immunotherapy approach with limited off-target effects. However, most peptides predicted using MHC binding prediction algorithms do not induce a CD8 + T cell response, and there is a crucial need to refine the predictions to readily identify the best antigens that could mediate T-cell responses. Such a response requires a high enough number of epitopes bound to the target MHC. This number is correlated with both the peptide-MHC binding affinity and the number of peptides reaching the ER. Beyond this, the response may be affected by the properties of the neo-epitope mutated residues.

Authors

  • Hanan Besser
    The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, 5290002, Ramat Gan, Israel.
  • Sharon Yunger
    Ella Lemelbaum Institute for Immuno Oncology, Sheba Medical Center, Ramat Gan, Israel.
  • Efrat Merhavi-Shoham
    Ella Lemelbaum Institute for Immuno Oncology, Sheba Medical Center, Ramat Gan, Israel.
  • Cyrille J Cohen
    Laboratory of Tumor Immunology and Immunotherapy, Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. cohency@biu.ac.il.
  • Yoram Louzoun
    Department of Mathematics, Bar-Ilan University, Ramat-Gan, Israel.

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