HSV-1 Oncolytic Virus Targeting CEACAM6-Expressing Tumors Using a Bispecific T-Cell Engager

Abstract

AbstractVG21306 is a novel oncolytic virus (OV) that encodes a secretable bispecific T-cell engager targeting Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6)-expressing tumors. Delivering a T-cell engager locally to a tumor mass will circumvent physical barriers that prevent antibodies from penetrating the tumor, and will mitigate the off-tumor, on-target toxicity risk. Both in vitro and in vivo testing demonstrated the expression of a functional T-cell engager capable of binding both targets. The efficacy of the engager was demonstrated in vitro, where addition of the engager payload to the OV enhanced anti-tumor efficacy against tumor cells overexpressing CEACAM6. Moreover, we have demonstrated the engager’s ability to induce bystander killing in cells lacking CEACAM6 expression, as well as engaging exhausted T cells and inducing tumor cell death. The safety of the engager was demonstrated by the lack of binding to normal human tissue or normal tissue adjacent to tumors, as well as the absence of any measurable leakage of the expressed engager into the blood of mice treated by intratumoral OV injection.