Vaccine-mediated cancer treatment is generally insufficient to bestow long-term survival unless suppressive mechanisms are overcome. Given the success of antibody-mediated immune checkpoint blockade in relieving suppression of anti-tumor T cell responses that develop naturally in tumor-burdened hosts, we investigated whether checkpoint blockade can be used to improve the efficacy of vaccine-induced T cell responses. Combining an adjuvanted whole-cell vaccine with antibodies to cytotoxic T lymphocyte antigen-4 (α-CTLA-4) resulted in regression of established intracranial tumors, whereas neither treatment was effective as a monotherapy. In contrast, combining the vaccine with antibodies to programmed death-1 (α-PD-1) failed to provide any survival advantage despite α-PD-1 being effective against the same tumor implanted subcutaneously, which was attributed to poor access of α-PD-1 to T cell effectors in the brain. The effective combination of vaccine and α-CTLA-4 was associated with enhanced proliferation and accumulation of T cells in the lymphoid tissues without any obvious changes in the stimulatory function of antigen-presenting cells or the number of regulatory T cells, suggesting recently primed T cells were the targets of checkpoint inhibition. While tumors regressing under this combined treatment were highly infiltrated with a variety of leukocytes, tumor eradication was strictly dependent on CD4+ T cells. These results demonstrate that vaccination can be combined effectively with checkpoint blockade to induce effective T cell-mediated responses against glioma. However, new strategies are required to improve access of inhibitors to the brain if immune checkpoints on intratumoral effector cells are to be targeted.

Citation Format: Cameron S. Field, Martin K. Hunn, Peter M. Ferguson, Hideo Yagita, Ian F. Hermans, Lindsay R. Ancelet. Tumor eradication in a murine model of glioma with vaccination and anti-CTLA-4 but not anti-PD-1. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B127.