An innovative non-mutant neoepitopes-based immunotherapy targeting immune-escaped tumors – NEOCOMBO

Although promising, immunotherapies targeting PD-1 are effective in only a fraction of cancer patients and the mechanisms associated with resistance are poorly elucidated. Indeed, tumors use additional pathways to evade CD8 T-cell recognition in particular alterations in peptide transporters TAP. We previously identified a non-mutant tumor neoepitope derived from ppCT and processed independently of TAP. We also developed an active immunotherapy based on ppCT able to control growth of immune-escaped tumors. Our objective is to validate a combination immunotherapy based on the ppCT vaccine and anti-PD-1. We will optimize it by identifying long ppCT peptides and undertake preclinical toxicology study. We will also identify novel non-mutant tumor neoepitopes from leader sequences of self-proteins expressed in anti-PD-1-responder tumors displaying low levels of TAP, investigate their involvement in the response to anti-PD-1 and then include them in the vaccine to eliminate resistant tumors.