High-affinity peptide-based anticancer vaccination to overcome resistance to immunostimulatory antibodies.

ABSTRACT

We tested how to eradicate long-established immunogenic tumors that were resistant to the monoclonal antibody-mediated blockade of PD-L1 (PD-1 ligand 1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Bacterial vaccination with a tumor-specific peptide exhibiting a high affinity for its respective MHC molecule consistently eradicated tumors when combined with a PD-L1 blocking antibody. This approach can be translated to the clinic by combining cancer cell whole-exome sequencing with algorithms to identify mutant peptides with high peptide-MHC binding affinity.