Journal
CANCER LETTERS
Volume 339, Issue 2, Pages 195-207Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.06.009
Keywords
T-CM; CD8(+)T cell; TCR; Transfer; Immunotherapy
Categories
Funding
- National Major Projects of Science and Technology of China [2009ZX09103-708]
- National Natural Science Foundation of China [31100664]
- Natural Science Foundation of Guangdong Province China [10151022401000024]
- Science and Technology Planning Project of Guangdong Province, China [2004B31201001, 2012A061400021]
Ask authors/readers for more resources
Adoptive cell therapy provides an attractive treatment of cancer, and our expanding capacity to target tumor antigens is driven by genetically engineered human T lymphocytes that express genes encoding tumor-specific T cell receptors (TCRs). The intrinsic properties of cultured T cells used for therapy were reported to have tremendous influences on their persistence and antitumor efficacy in vivo. In this study, we isolated CD8(+) central memory T cells from peripheral blood lymphocytes of healthy donors, and then transferred with the gene encoding TCR specific for tumor antigen using recombinant adenovirus vector Ad5F35-TRAV-TRBV. We found effector T cells derived from central memory T cells improved cell viability, maintained certain level of CD62L expression, and reacquired the CD62L(+)CD44(high) phenotype of central memory T cells after effector T cells differentiation. We then compared the antitumor reactivity of central memory T cells and CD8(+)T cells after TCR gene transferred. The results indicated that tumor-specific TCR gene being transferred to central memory T cells effectively increased the specific killing of antigen positive tumor cells and the expression of cytolytic granule protein. Furthermore, TCR gene transferred central memory T cells were more effective than TCR gene transferred CD8(+)T cells in CTL activity and effector cytokine secretion. These results implicated that isolating central memory T cells rather than CD8(+)T cells for insertion of gene encoding tumor-specific TCR may provide a superior tumor-reactive T cell population for adoptive transfer. (C) 2013 Published by Elsevier Ireland Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available