Transfer of TCR genes into mature T cells is accompanied by the maintenance of parental T cell avidity.
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.
Rubinstein
Mark P
MP
Department of Surgery, Section of Surgical Oncology, Medical University of South Carolina, Charleston, SC 29425, USA.
Kadima
Andre N
AN
Salem
Mohamed L
ML
Nguyen
Christophe L
CL
Gillanders
William E
WE
Nishimura
Michael I
MI
Cole
David J
DJ
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D004527:Egg Proteins / Q000235:genetics / Q000276:immunology; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000276:immunology; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D014161:Transduction, Genetic / Q000379:methods*; D014407:Tumor Cells, Cultured
D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin