Translating B-Cell Epitope Peptide-Based Cancer Vaccines to the Clinic Immunotherapies

Blockade of checkpoint receptors with monoclonal antibodies have shown great clinical success, but some patients develop resistance and remain refractory. Both PD-1/PD-L1 and HER-2 inhibitors have limited efficacy and toxicities. Ongoing clinical studies support the need for combination immuno-oncology agents to save the lives of patients. We introduce a novel PD-L1 B-cell peptide vaccine linked to a “promiscuous” T cell MVF peptide (PDL1-Vaxx) or linked to TT3 via a linker. These vaccines are highly immunogenic and antigenic in animal models. The PD-L1 vaccines elicited high titers of antibodies that inhibit tumor growth, induced PD-1/PD-L1 blockade, decreased proliferation, induced apoptosis and caused ADCC of tumor cells. The combination of PDL1-Vaxx with HER-2 vaccine (B-Vaxx) demonstrated tumor inhibition in D2F2/E2 carcinoma. The anti-PDL1-Vaxx block PD-1/PD-L1 interaction and significantly prolonged anti-tumor responses. The combination of B-Vaxx with either PDL1-Vaxx or PD1-Vaxx demonstrated tumor inhibition. PDL1-Vaxx is a promising safe checkpoint inhibitor vaccine.