The use of chimeric human FcE receptor I to redirect cytotoxic T lymphocytes to tumors

Abstract: Chimeric receptors that redirect effector cell function to tumor cells or virus-infected cells have received much attention. Given the high affinity of FccRI for immunoglobulin E (IgE) and low serum IgE levels, redirection of effector cells using Fcs receptor may provide a novel, versatile, and effective anti-tumor strategy. We have used a mouse perform 5’-promoter to express a single-chain human FcE receptor in the mouse cytotoxic T lymphocyte cell line, CTLL-R8. Upon ligation of the chimeric FcE receptors by IgE, a signal for effector function is transmiUed via the intra-cellular domain ofCD3#{231} Selection in G418-containing medium produced CTLL-R8 transfectant clones that: (1) expressed chimeric FcE receptor as determined by flow cytometry; (2) bound human IgE antibodies with high affinity as determined by Scatchard analysis; (3) specifically rosetted IgE-coated SRBC; (4) lysed tar-get cells in IgE-mediated ADCC and reverse ADCC assays; and (5) retarded tumor growth in a Winn as-say. Therefore these chimeric FeE receptors can effec-lively redirect cytotoxicity to tumor cells. Future efforts will assess the versatility and efficacy of these IgE-binding chimeric receptors to redirect killer cell func-tion in animal tumor models. J. Leukoc. Biol. 60