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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Moeller, Maria Teng, Michele W. L. Darcy, Phillip K. Prince, H. Miles Scott, Andrew M. Smyth, Fiona E. Power, Barbara E. Cartwright, Glenn A. Westwood, Jennifer A. Kershaw, Michael H. Smyth, Mark J. Hönemann, Dirk Trapani, Joseph A. |
| Description | Author Affiliation: Westwood JA ( Cancer Immunology Program and Department of Hematology and Medical Oncology, Peter MacCallum Cancer Centre, St. Andrew's Place, Melbourne, Victoria 3002, Australia.); |
| Abstract | In this study, human T cells were provided with a reactivity against the Lewis-Y (Le(Y)) carbohydrate antigen, which is overexpressed on 70% of epithelial-derived tumors, but not normally recognized by T cells. Antitumor reactivity was achieved by transduction of T cells with a gene encoding a cell-surface chimeric receptor composed of single-chain anti-Le(Y) antibody linked to an enhanced cytoplasmic signaling domain made up of CD28 and CD3-zeta. Importantly, the single-chain antibody was humanized to try to reduce potential problems of human anti-mouse antibody responses in patients receiving chimeric receptor-modified T cells in future clinical trials. T cells expressing the chimeric receptor were demonstrated to secrete cytokines and proliferate in response to receptor ligation and lysed Le(Y+) tumors in vitro. Another aspect of this study was the finding that no activity was observed against normal tissue, as represented by autologous neutrophils that express low levels of Le(Y). Significantly, systemic delivery of anti-Le(Y) T cells dramatically inhibited established s.c. human ovarian OVCAR-3 tumors (a recognized difficult model to treat) in mice. Finally, we demonstrated that anti-Le(Y) T cells preferentially expanded or accumulated in the tumor compared with control empty vector T cells, thereby providing mechanistic insight into the specific antitumor response. This study supports the use of humanized gene-modified T cells as a potential therapy for Le(Y+) malignancies. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 52 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Adoptive Transfer Immunotherapy Lewis Blood-Group System Chemistry Receptors, Antigen, T-Cell Physiology T-Lymphocytes Cytology Animals Antigens, CD Biosynthesis Antigens, CD28 Antigens, Differentiation, Myelomonocytic Autoimmunity Cell Line, Tumor Cell Membrane Metabolism Cell Proliferation Clinical Trials As Topic Cytokines Flow Cytometry Genetic Vectors Immunohistochemistry Leukocytes, Mononuclear Mice Neoplasm Transplantation Neoplasms Neutrophils Recombinant Fusion Proteins Retroviridae Genetics Sialic Acid Binding Ig-like Lectin 3 Time Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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