PMID- 8975874 OWN - NLM STAT- MEDLINE DCOM- 19970122 LR - 20190516 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 60 IP - 6 DP - 1996 Dec TI - The use of chimeric human Fc(epsilon) receptor I to redirect cytotoxic T lymphocytes to tumors. PG - 721-8 AB - 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. FAU - Kershaw, M H AU - Kershaw MH AD - Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia. FAU - Darcy, P K AU - Darcy PK FAU - Trapani, J A AU - Trapani JA FAU - Smyth, M J AU - Smyth MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (CD3 Complex) RN - 0 (Membrane Glycoproteins) RN - 0 (Pore Forming Cytotoxic Proteins) RN - 0 (Receptors, IgE) RN - 0 (Recombinant Fusion Proteins) RN - 126465-35-8 (Perforin) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Animals MH - Antibody-Dependent Cell Cytotoxicity MH - CD3 Complex/chemistry MH - Cytotoxicity, Immunologic MH - Dose-Response Relationship, Immunologic MH - Humans MH - Immunoglobulin E/immunology MH - Immunotherapy MH - Membrane Glycoproteins/genetics MH - Mice MH - Mice, Inbred C57BL MH - Neoplasms, Experimental/*therapy MH - Perforin MH - Pore Forming Cytotoxic Proteins MH - Receptors, IgE/*chemistry/immunology MH - Recombinant Fusion Proteins MH - T-Lymphocytes, Cytotoxic/*immunology MH - Transfection EDAT- 1996/12/01 00:00 MHDA- 1996/12/01 00:01 CRDT- 1996/12/01 00:00 PHST- 1996/12/01 00:00 [pubmed] PHST- 1996/12/01 00:01 [medline] PHST- 1996/12/01 00:00 [entrez] AID - 10.1002/jlb.60.6.721 [doi] PST - ppublish SO - J Leukoc Biol. 1996 Dec;60(6):721-8. doi: 10.1002/jlb.60.6.721.