Cancer immunotherapy with checkpoint inhibitors has resulted in impressive clinical results in several cancer indications. Despite this success, only a fraction of patients show durable and complete response to blockade by ipilimumab, an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb. We identified four CTLA-4 peptide sequences from which engineered chimeric B-cell epitope constructs incorporating a "promiscuous" T-cell epitope elicited highly immunogenic anti-CTLA-4 natural polyclonal antibodies by immunization. Combination of CTLA-4 peptide vaccine with other checkpoint inhibitor vaccines PD1-Vaxx or PDL1-Vaxx was investigated in several breast and colon carcinoma BALB/c syngeneic models (CT26, 4T1, and D2F2). CTLA-4 vaccines showed significant tumor suppression and prolonged survival rates as compared with anti-mouse CTLA-4 mAb 9H10. The resulting antipeptide antibodies suppressed tumor proliferation and migration similar to ipilimumab. We focused on one CTLA-4 epitope sequence 130 to 150 that embodies the "MYPPPY" motif that ipilimumab binds to. Combination of MVF-CTLA-4 (130-150) with either PD1-Vaxx or PDL1-Vaxx showed synergistic activity. The 130 to 150 peptide mimic demonstrated that the polyproline type II helix motif showed inhibition of tumor growth and therapeutic efficacy in the syngeneic CT26/BALB/c model. Several CTLA-4 vaccines have been identified that show synergistic activities with other checkpoint inhibitor vaccines to PD1 and PDL1.