Expression in cytotoxic T lymphocytes of a single-chain anti-carcinoembryonic antigen antibody. Redirected Fas ligand-mediated lysis of colon carcinoma

Abstract

In the MD45 mouse cytotoxic T lymphocyte (CTL) hybridoma cell line, we have expressed a chimeric receptor, consisting of the single-chain variable domains (scFv) of anti-carcinoma embryonic antigen (CEA) mAb linked to Fcγ receptor (FcγR) chain via a CD8 hinge. Transfected MD45 subclones lysed CEA-positive human colon carcinoma cell lines in an antigen-specific and FasL-dependent manner. The degree of lysis correlated with the level of chimeric receptor expressed on transduced MD45 subclones. The requirement for an intact Y65TGL motif in the signaling γ chain suggested that interaction of the chimeric receptor with target cell CEA induced the cytotoxicity of MD45-scFv subclones. However, MD45..