620. Cancer Associated Fibroblasts-Targeted Oncolytic Virus Results in Enhanced Antitumor Activity in Mouse Model

Abstract

Oncolytic vaccinia virus (VV) therapy has shown promise in preclinical models and in clinical studies. However, complete responses have rarely been observed. Targeting cancer-associated fibroblasts (CAFs) in addition to cancer cells may enhance antitumor effects, since CAFs, the central component of the tumor stroma, directly support tumor growth and contribute to the immunosuppressive tumor microenvironment. To target CAFs we developed a new oncolytic vaccinia virus that encodes a secretory bispecific T-cell engager consisting of two single- chain variable fragments specific for CD3 and the fibroblast activation protein (FAP) (FAP-T-cell engager-armed VV (FAP-TEA-VV)). FAP-TEA-VV induced robust FAP- and TRP2-specific T-cell responses in tumor environment, resulting in greater antitumor activity in the B16 melanoma model in comparison to unmodified VVs. FAP-TEA-VV enhanced tumor infiltration of CD8-positive T cells, and enhanced virus spread with tumors. Thus, targeting of CAFs has the potential to improve current virus therapy for cancer.