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Title: The use of chimeric human Fc(epsilon) receptor I to redirect cytotoxic T lymphocytes to tumors.
Austin Authors: Kershaw, M H;Darcy, P K;Trapani, Joseph A;Smyth, Mark J
Affiliation: Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Dec-1996
Publication information: Journal of Leukocyte Biology; 60(6): 721-8
Abstract: Chimeric receptors that redirect effector cell function to tumor cells or virus-infected cells have received much attention. Given the high affinity of Fc(epsilon)RI for immunoglobulin E (IgE) and low serum IgE levels, redirection of effector cells using Fc(epsilon) 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(epsilon) receptor in the mouse cytotoxic T lymphocyte cell line, CTLL-R8. Upon ligation of the chimeric Fc(epsilon) receptors by IgE, a signal for effector function is transmitted via the intracellular domain of CD3zeta. Selection in G418-containing medium produced CTLLR8 transfectant clones that: (1) expressed chimeric Fc(epsilon) 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(epsilon) 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.
Gov't Doc #: 8975874
Journal: Journal of leukocyte biology
Type: Journal Article
Subjects: Animals
Antibody-Dependent Cell Cytotoxicity
Antigens, CD3.chemistry
Cytotoxicity, Immunologic
Dose-Response Relationship, Immunologic
Immunoglobulin E.immunology
Membrane Glycoproteins.genetics
Mice, Inbred C57BL
Neoplasms, Experimental.therapy
Pore Forming Cytotoxic Proteins
Receptors, IgE.chemistry.immunology
Recombinant Fusion Proteins
T-Lymphocytes, Cytotoxic.immunology
Appears in Collections:Journal articles

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