Abstract 3524: A novel approach to targeting mutated colorectal adenocarcinomas with T cell-engaging CEA/CD3-bispecific BiTE investigational antibody MEDI-565

Abstract

Abstract Colorectal cancer (CRC) cells can harbor somatic mutations with strong impact on cancer cell signaling that limit the effectiveness of both chemotherapy and targeted therapies including monoclonal antibodies and kinase inhibitors. Therefore, novel therapeutic modalities are needed that are not impacted by the presence of such genetic mutations. We have here evaluated a CEA/ CD3-bispecific BiTE antibody termed MEDI-565 (also known as MT111) for its ability to redirect cytotoxic T cells for lysis in co-cultures and in xenograft models of human CRC lines harboring oncogenic mutations. Redirected lysis of CEA-positive tumor cells by MEDI-565 occurred in a manner dependent on CEA surface antigen density but independent of exogenously added soluble CEA. Importantly, the potency of lysis was independent of the mutational status of genes commonly mutated or lost in colorectal and other cancers, including frequent mutations in KRAS, BRAF, PI3KCA, PTEN and TP53 genes. In mouse xenograft models, the ability of MEDI-565 to inhibit tumor growth was likewise independent of the mutational status of the human tumor xenograft models. Our findings suggest that MEDI-565 warrants further clinical investigation as a potential treatment option for patients with CEA-positive tumors harboring somatic mutations that are less responsive to traditional chemotherapy or targeted agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3524. doi:1538-7445.AM2012-3524