[HTML][HTML] Generation of diffuse large B cell lymphoma-associated antigen-specific Vα6/Vβ13+ T cells by TCR gene transfer

Q Yin, X Zha, L Yang, S Chen, Y Zhou, X Wu… - Journal of Hematology & …, 2011 - Springer
Q Yin, X Zha, L Yang, S Chen, Y Zhou, X Wu, Y Li
Journal of Hematology & Oncology, 2011Springer
Background Our previous study had amplified antigen-specific full-length TCR α and β
genes of clonally expanded T cells in the peripheral blood (PB) of patients with diffuse large
B-cell lymphoma (DLBCL). The transfer of T cell receptor (TCR) genes endows T cells with
new antigen specificity. Therefore, the aim of this study is to generate diffuse large B cell
lymphoma (DLBCL)-specific T cells by T cell receptor (TCR) gene transfer. Materials and
methods Two different eukaryotic expression plasmids harboring TCR Vα6 and TCR Vβ13 …
Background
Our previous study had amplified antigen-specific full-length TCR α and β genes of clonally expanded T cells in the peripheral blood (PB) of patients with diffuse large B-cell lymphoma (DLBCL). The transfer of T cell receptor (TCR) genes endows T cells with new antigen specificity. Therefore, the aim of this study is to generate diffuse large B cell lymphoma (DLBCL)-specific T cells by T cell receptor (TCR) gene transfer.
Materials and methods
Two different eukaryotic expression plasmids harboring TCR Vα6 and TCR Vβ13 genes specific for DLBCL-associated antigens were constructed and subsequently transferred into human T cells using Nucleofector™ technique. The expression of targeted genes in TCR gene-modified cells was detected by real-time PCR, and western blot using TCR Vβ antibody. The specific cytotoxicity of TCR gene-transferred T cells in vitro was estimated using a lactate dehydrogenase (LDH) release assay.
Results
Two different eukaryotic expression plasmids harboring TCR Vα6 and TCR Vβ13 genes specific for DLBCL-associated antigens were constructed and subsequently transferred into T cells from healthy donors. Specific anti-DLBCL cytotoxic T lymphocytes (CTL) could be induced by transduction of specific TCR gene to modify healthy T cells. The transgene cassette of TCR Vβ13-IRES-TCR Vα6 was superior to the other in the function of TCR-redirected T cells.
Conclusions
Specific anti-DLBCL cytotoxic T lymphocyte (CTL) could be inducted by transduction of specific TCR gene to modify healthy T cells.
Springer