| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Chain Genes Isolated from a Clonally Expanded P815-Infiltrating Lymphocyte1
* Department of Allergy and Rheumatology, Graduate School of Medicine, and
Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Gene transfer of TCR 
-chains into T cells may be a promising strategy for providing valuable T lymphocytes in the treatment of tumors and other immune-mediated disorders. We report in this study the reconstitution of CD8+ T cells by transfer of TCR -chain genes derived from an infiltrating T cell into P815. Analysis of the clonal expansion and V subfamily usage of CD8+ TIL in the tumor sites demonstrated that T cells using V10 efficiently infiltrated and expanded clonally. The TCR - and -chain sequences derived from a tumor-infiltrating CD8+/V10+ single T cell clone (P09-2C clone) were simultaneously determined by the RT-PCR/single-strand conformational polymorphism method and the single-cell PCR method. When P09-2C TCR -chain genes were retrovirally introduced into CD8+ T cells, the reconstituted T cells positively lysed the P815 tumor cells, but not the A20, EL4, or YAC-1 cells, in vitro. In addition, the CTL activity was blocked by the anti-H2Ld mAb. Furthermore, T cells containing both TCR - and -chains, but not TCR -chain alone, accumulated at the tumor-inoculated site when the reconstituted CD8+ T cells were adoptively transferred to tumor-bearing nude mice. These findings suggest that it is possible to reconstitute functional tumor-specific CD8+ T cells by transfer of TCR -chain genes derived from TIL, and that such T cells might be useful as cytotoxic effector cells or as a vehicle for delivering therapeutic agents.
This article has been cited by other articles:
|
|
 |
|
  S. Thomas, S.-A. Xue, M. Cesco-Gaspere, E. San Jose, D. P. Hart, V. Wong, R. Debets, B. Alarcon, E. Morris, and H. J. Stauss Targeting the Wilms Tumor Antigen 1 by TCR Gene Transfer: TCR Variants Improve Tetramer Binding but Not the Function of Gene Modified Human T Cells J. Immunol., November 1, 2007; 179(9): 5803 - 5810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fujio, A. Okamoto, Y. Araki, H. Shoda, H. Tahara, N. H. Tsuno, K. Takahashi, T. Kitamura, and K. Yamamoto Gene Therapy of Arthritis with TCR Isolated from the Inflamed Paw J. Immunol., December 1, 2006; 177(11): 8140 - 8147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Seitz, C. K. Schneider, J. Malotka, X. Nong, A. G. Engel, H. Wekerle, R. Hohlfeld, and K. Dornmair Reconstitution of paired T cell receptor {alpha}- and beta-chains from microdissected single cells of human inflammatory tissues PNAS, August 8, 2006; 103(32): 12057 - 12062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-A. Xue, L. Gao, D. Hart, R. Gillmore, W. Qasim, A. Thrasher, J. Apperley, B. Engels, W. Uckert, E. Morris, et al. Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene-transduced human T cells Blood, November 1, 2005; 106(9): 3062 - 3067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Morris, A. Tsallios, G. M. Bendle, S.-a. Xue, and H. J. Stauss A critical role of T cell antigen receptor-transduced MHC class I-restricted helper T cells in tumor protection PNAS, May 31, 2005; 102(22): 7934 - 7939. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
