Premium
The use of chimeric human Fcε receptor I to redirect cytotoxic T lymphocytes to tumors
Author(s) -
Kershaw Michael H.,
Darcy Phillip K.,
Trapani Joseph A.,
Smyth Mark J.
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.60.6.721
Subject(s) - antibody dependent cell mediated cytotoxicity , biology , receptor , cytotoxic t cell , immunoglobulin e , fc receptor , microbiology and biotechnology , effector , fragment crystallizable region , antibody , immunology , cytolysis , flow cytometry , cancer research , monoclonal antibody , in vitro , biochemistry
Chimeric receptors that redirect effector cell function to tumor cells or virus‐infected cells have received much attention. Given the high affinity of FcRI for immunoglobulin E (IgE) and low serum IgE levels, redirection of effector cells using Fc receptor may provide a novel, versatile, and effective anti‐tumor strategy. We have used a mouse perforin 5'‐promoter to express a single‐chain human Fc receptor in the mouse cytotoxic T lymphocyte cell line, CTLL‐R8. Upon ligation of the chimeric Fc receptors by IgE, a signal for effector function is transmitted via the intracellular domain of CD3. Selection in G418‐contaming medium produced CTLL‐R8 transfectant clones that: (1) expressed chimeric Fc 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 target cells in IgE‐mediated ADCC and reverse ADCC assays; and (5) retarded tumor growth in a Winn assay. Therefore these chimeric Fc receptors can effectively redirect cytotoxicity to tumor cells. Future efforts will assess the versatility and efficacy of these IgE‐binding chimeric receptors to redirect killer cell function in animal tumor models. J. Leukoc. Biol . 60: 721–728; 1996.