Redirecting mouse CTL against colon carcinoma: Superior signaling efficacy of single-chain variable domain chimeras containing TCR-ζ vs FcεRI-γ

Abstract

The structurally related TCR-ζ and Fc receptor for IgE (FcεRI)-γ are critical signaling components of the TCR and FcεRI, respectively. Although chimeric Ab receptors containing ζ and γ signaling chains have been used to redirect CTL to tumors, a direct comparison of their relative efficacy has not previously been undertaken. Here, in naive T lymphocytes, we compare the signaling capacities of the ζ and γ subunits within single-chain variable domain (scFv) chimeric receptors recognizing the carcinoembryonic Ag (CEA). Using a very efficient retroviral gene delivery system, high and equivalent levels of scFv-ζ and scFv-γ receptors were expressed in T cells. Despite similar levels of expression ..