RT Journal Article
SR Electronic
T1 Efficient Transfer of a Tumor Antigen-Reactive TCR to Human Peripheral Blood Lymphocytes Confers Anti-Tumor Reactivity
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 507
OP 513
VO 163
IS 1
A1 Clay, Timothy M.
A1 Custer, Mary C.
A1 Sachs, Jessica
A1 Hwu, Patrick
A1 Rosenberg, Steven A.
A1 Nishimura, Michael I.
YR 1999
UL http://www.jimmunol.org/content/163/1/507.abstract
AB The tumor-associated-Ag MART-1 is expressed by most human melanomas. The genes encoding an αβ TCR from a MART-1-specific, HLA-A2-restricted, human T cell clone have been efficiently transferred and expressed in human PBL. These retrovirally transduced PBL cultures were MART-1 peptide reactive, and most cultures recognized HLA-A2+ melanoma lines. Limiting dilution clones were generated from three bulk transduced PBL cultures to investigate the function of individual clones within the transduced cultures. Twenty-nine of 29 CD8+ clones specifically secreted IFN-γ in response to T2 cells pulsed with MART-1(27–35) peptide, and 23 of 29 specifically secreted IFN-γ in response to HLA-A2+ melanoma lines. Additionally, 23 of 29 CD8+ clones lysed T2 cells pulsed with the MART-1(27–35) peptide and 15 of 29 lysed the HLA-A2+ melanoma line 888. CD4+ clones specifically secreted IFN-γ in response to T2 cells pulsed with the MART-1(27–35) peptide. TCR gene transfer to patient PBL can produce CTL with anti-tumor reactivity in vitro and could potentially offer a treatment for patients with metastatic melanoma. This approach could also be applied to the treatment of other tumors and viral infections. Additionally, TCR gene transfer offers unique opportunities to study the fate of adoptively transferred T cells in vivo.