biostudies-literatureHailemichael YUT MD Anderson Cancer Center SPORE in Melanoma grant from NCINANIAID NIH HHSNCI NIH HHSCancer Prevention and Research Institute of Texas1338-1354https://www.ebi.ac.uk/biostudies/studies/S-EPMC5873868biostudies-literatureUnknown128(4)Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control. The inflamed vaccination site subsequently also sequestered and destroyed anti-CTLA-4-induced Teffs with specificities for tumor antigens other The Journal of clinical investigationCancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy.PMC5873868NARP140522P50 CA093459T32 AI007496P30 CA044579Fu TSharma PHasan FXiao ZKhong HHailemichael YRoszik JSchluns KSVianden CHe QAnthony SMDai ZSharma MWoods ANielsen MCOverwijk WWSingh MEngelhard VHFaak FMoore DfalseCancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy.Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control. The inflamed vaccination site subsequently also sequestered and destroyed anti-CTLA-4-induced Teffs with specificities for tumor antigens other 2018-01-01T00:00:00Z2018 Apr2026-05-05T23:35:01.296Z2019-03-26T23:44:12ZS-EPMC58738682948081710.1172/jci9330310.1172/JCI93303