Transfer of TCR Genes into Mature T Cells Is Accompanied by the Maintenance of Parental T Cell Avidity
| Autor: | Mohamed L. Salem, David J. Cole, Andre N. Kadima, William E. Gillanders, Michael I. Nishimura, Mark P. Rubinstein, Christophe L. Nguyen |
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| Rok vydání: | 2003 |
| Předmět: |
Cytotoxicity
Immunologic Adoptive cell transfer Ovalbumin Receptors Antigen T-Cell alpha-beta T cell Genetic Vectors Immunology Mice Transgenic chemical and pharmacologic phenomena Streptamer Biology Mice Antigen T-Lymphocyte Subsets Transduction Genetic Tumor Cells Cultured medicine Animals Immunology and Allergy Cytotoxic T cell Avidity Cells Cultured Egg Proteins T-cell receptor Cell Differentiation Molecular biology Peptide Fragments Mice Inbred C57BL medicine.anatomical_structure Genes T-Cell Receptor beta Moloney murine leukemia virus Clone (B-cell biology) Genes T-Cell Receptor alpha |
| Zdroj: | The Journal of Immunology. 170:1209-1217 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.170.3.1209 |
| Popis: | The adoptive transfer of tumor-specific T cells expanded in vitro can be of significant therapeutic value in select cancer patients. This strategy is limited though, as it is often difficult, if not impossible, to obtain T cells of clinical value. The transfer of TCR genes to mature T cells to generate tumor-reactive T cells provides a potential mechanism to overcome these limitations. To evaluate the feasibility of such an approach and the quality of the resulting T cells, we generated replication-deficient retroviral vectors using the well-characterized OT-1 TCR genes. After transducing murine T cells, we were able to expand large numbers of Ag-specific T cells that were functionally active against tumor cells expressing the relevant Ag. Furthermore, we found that T cells expressing retrovirally encoded TCR had avidity that was similar to that of the parental clone. This maintenance of avidity was despite variable expression of the retrovirally encoded TCR and the presence of potentially competing endogenous TCRs. These results suggest that the inherent qualities of the TCR, as dictated by the coding sequence, are the most critical parameters in the generation of high-avidity T cells. |
| Databáze: | OpenAIRE |
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