Abstract 2505: Therapeutic efficacy of the ZVex™ and GLAAS™ platforms in a B16-F10/hCAIX melanoma mouse model

Abstract

Abstract ZVex™ and GLAAS™ are two dendritic-cell (DC) targeting platform technologies designed to enhance immune responses through the in vivo induction of antigen specific CD8 and CD4 T-cells, respectively. ZVex™ is a lentiviral vector pseudotyped with a modified Sindbis virus envelope engineered to deliver tumor antigen-encoding nucleic acids to dendritic cells in vivo. GLAAS™(Glucopyranosyl Lipid A Adjuvant System) activates DC by binding to the TLR-4 receptor and inducing strong Th1 type CD4 responses against co-delivered recombinant proteins. Currently both platform technologies are being investigated in phase I clinical trials in cancer patients. Human carbonic anhydrase 9 (hCAIX) is a tumor-associated transmembrane antigen that is over-expressed on various cancer cell types. We mapped hCAIX specific, multi-functional CD8 and CD4 T-cell epitopes within the extracellular and transmembrane regions of the protein for the mouse haplotype H-2b by intracellular cytokine staining. Mice lethally challenged s.c. on the flank with a B16-F10 tumor cell line expressing the hCAIX protein (designated BC.12) fully controlled large tumors (>100 mm2) when therapeutically immunized (subcutaneously at the base of tail) with ZVex™ encoding hCAIX or the recombinant hCAIX protein with GLAAS™ (either s.c. or i.m.). In both models, tumor control was dose-dependent. Additionally, the presence of a strong transmembrane H-2b restricted CD8 T-cell epitope was required for tumor control and regression. hCAIX-specific CD8 T-cell responses were detectable as far out as day 67 post challenge in mice displaying full regression of tumor. These results demonstrate proof of concept for ZVex™ and GLAAS™ platform technologies in an aggressive murine melanoma model. Citation Format: David J. Campbell, Rebecca S. Reeves, Patrick A. Flynn, Scott H. Robbins, Peter Berglund, Jan H. ter Meulen. Therapeutic efficacy of the ZVex™ and GLAAS™ platforms in a B16-F10/hCAIX melanoma mouse model. [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 2505. doi:10.1158/1538-7445.AM2015-2505