Redirected perforin-dependent lysis of colon carcinoma by ex vivo genetically engineered CTL

Abstract

The redirection of autologous lymphocytes to predefined tumor target Ags has considerable potential for the immunotherapeutic treatment of cancer; however, robust experimental systems for comparing various approaches have not been developed. Herein, we have generated a single chain variable domain anti-carcinoembryonic Ag (CEA) Fcε receptor I γ-chain fusion (scFv anti- CEA) receptor and demonstrated high-level expression of this chimeric receptor in naive mouse T lymphocytes by retroviral gene transduction. These gene-modified CTL were able to lyse CEA+ targets and secrete high levels of IFN-γ following Ag stimulation. Depletion studies demonstrated that specific tumor cell cytotoxicity was ..