Abstract 2517: Effects of toll-like receptor 4 agonist on the anti-tumor immune response to the GVAX vaccine

Abstract

Abstract We evaluated the immune response elicited by co-administration of a novel toll-like receptor 4 agonist, glucopyranosyl lipid A (GLA), with a genetically modified tumor cell based vaccine (GVAX) in mice. We have previously reported that the addition of GLA to the GVAX vaccine in mice resulted in a paradoxical decrease in delivery of tumor antigen to the draining lymph node, yet an increase in therapeutic benefit. The addition of GLA to GVAX altered the distribution of the vaccine induced anti-tumor T cell response. In mice vaccinated with GVAX + GLA adjuvant tumor-specific T cells accumulated in the spleen, liver and footpad as soon as two days following vaccination. In contrast, in mice vaccinated with GVAX alone, tumor-specific T cells accumulated primarily only in the dLN. Since our previous study established that incorporation of GLA into the GVAX vaccine did not alter the magnitude of the anti-tumor T cell response, we set out to determine if the co-administration of GLA with GVAX altered the functional capabilities of the anti-tumor T cell response. We found that GLA did not increase in vivo tumor-specific cytotoxic activity or increase the number of anti-tumor interferon-γ expressing T cells found in the tumor or spleen following vaccination. We next determined if the addition of GLA to GVAX altered the kinetics of the anti-tumor T cell response. We found that the addition of GLA to the GVAX vaccine resulted in rapid accumulation of activated anti-tumor T cells in the spleen. Our results suggest that addition of GLA to the GVAX vaccine does not increase the magnitude or significantly improve functional capabilities of the anti-tumor immune response. These findings are consistent with the hypothesis that the addition of GLA to the GVAX vaccine increases therapeutic benefit by altering the distribution of the response, resulting in a more systemic anti-tumor immune response. Citation Format: Michael J. Korrer, Jeff W.m. Bulte, Hyam I. Levitsky. Effects of toll-like receptor 4 agonist on the anti-tumor immune response to the GVAX vaccine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2517. doi:10.1158/1538-7445.AM2015-2517