Abstract 2388: In vitro assessment of tumor associated I.O. markers in cancer cell lines following Vicinium treatment

Abstract

Abstract Vicinium is a fusion protein that comprises a scFv fragment specific for the Epithelial Cell Adhesion Molecule (EpCAM) genetically fused to a truncated form of Pseudomonas exotoxin A, ETA, via a flexible linker. Vicinium is used for the treatment of loco-regionally accessible tumors and is currently in a phase III clinical trial (VISTA) for the treatment of high-grade non-muscle invasive bladder cancer and a phase I study in combination with durvalumab for the same indication. In a different phase I study in late stage squamous cell carcinoma of the head and neck, direct injection of Vicinium led to shrinkage of the principal injected tumor as well as non-targeted tumors in some patients suggesting the activation of a T cell-mediated anti-tumor response through cross-priming. Supporting this hypothesis, in vitro studies have demonstrated that Vicinium mediated tumor cell killing elicits biological features of an immunogenic cell death (ICD). Tumor cells’ ability to evade the innate and adaptive immune response plays a major role in cancer development and progression. Altered expression of immune modulators is a key mechanism responsible for tumor escape. Recent studies have shown that exposure to chemotherapeutic drugs results in the selection of tumor cells expressing immunosuppressive markers such as PD-L1, CD47 and CD39. Following in vitro treatment with Vicinium, the enrichment of tumor cell population expressing I.O. markers was examined and compared to chemotherapeutic agents. Unlike small molecule chemotherapies, Vicinium treatment did not lead to an enrichment of CD47 or CD39 positive tumor cell populations. Taken together, the data suggests that Vicinium does not induce an immunosuppressive environment. Citation Format: Shilpa Chooniedass, Rachelle L. Dillon, Arjune Premsukh, Glen C. MacDonald, Jeannick Cizeau, Gregory P. Adams. In vitro assessment of tumor associated I.O. markers in cancer cell lines following Vicinium treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2388.