Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/13499
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 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/13499 | Journal: | Journal of leukocyte biology | URL: | https://pubmed.ncbi.nlm.nih.gov/8975874 | Type: | Journal Article | Subjects: | Animals Antibody-Dependent Cell Cytotoxicity Antigens, CD3.chemistry Cytotoxicity, Immunologic Dose-Response Relationship, Immunologic Humans Immunoglobulin E.immunology Immunotherapy Membrane Glycoproteins.genetics Mice Mice, Inbred C57BL Neoplasms, Experimental.therapy Perforin Pore Forming Cytotoxic Proteins Receptors, IgE.chemistry.immunology Recombinant Fusion Proteins T-Lymphocytes, Cytotoxic.immunology Transfection |
Appears in Collections: | Journal articles |
Show full item record
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.