IMMU-31. PROTEASOME REARRANGED PEPTIDES ARE A NOVEL SOURCE OF ANTIGENS FOR THE PEPTIDE VACCINE IMMUNOTHERAPY OF GLIOBLASTOMAS

Abstract pepVIII, an anticancer vaccine targeting EGFRvIII, has been tested in several trials for glioblastoma including ACT IV. a randomized Phase III trial newly diagnosed patients. While results from IV were equivocal, available data suggests the elimination of EGFRvIII was not robust. Despite its essential role antigen presentation, enhancing proteasomal processing is unexploited strategy improving vaccines. We examined 20 peptides silico and experimentally, which showed that tyrosine substitution (Y6-pepVIII) maximizes proteasome cleavage survival subcutaneous tumor model. In intracranial glioma model, Y6-pepVIII 62 31% improvement median compared to control animals pepVIII-vaccinated mice. vaccination altered tumor-infiltrating lymphocyte subsets expression PD-1 on intratumoral T cells. Combination with anti–PD-1 therapy cured 45% Y6-pepVIII–vaccinated mice but ineffective pepVIII-treated LC-MS/MS analysis proteasome-digested pepVIII revealed most fragments similar more abundant inY6-pepVIII digests 77% resulted proteasome-catalyzed peptide splicing (PCPS). identified 10 bound human murine MHC class I. Nine PCPS products only one colinear indicating may be component I recognition. being two three capable increasing when administered independently as hypothesize immune response represents collective contribution multiple linear products. Our work increase augmented enhanced