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Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
The tumor-associated-Ag MART-1 is expressed by most human
melanomas. The genes encoding an 
ß 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-
in response to T2 cells pulsed with MART-1(27–35) peptide,
and 23 of 29 specifically secreted IFN- 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- 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.
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