Mike:
It's more complicated that just doing this, but I have to keep the central issues close to the vest. Or at least I'm going to do more of such, going forward. In any event, here's something that GZMO may of may have rights to (I haven't asked, but it's certainly complementary to the dendritic cell vaccine work from Rosenberg). Concepts similar to those in "practice" at CEGE, same complications........
J Immunol 1999 Jul 1;163(1):507-13
Efficient transfer of a tumor antigen-reactive TCR to human peripheral
blood lymphocytes confers anti-tumor reactivity.
Clay TM, Custer MC, Sachs J, Hwu P, Rosenberg SA, Nishimura MI
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
The tumor-associated-Ag MART-1 is expressed by most human melanomas. The genes encoding an alphabeta 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-gamma in response
to T2 cells pulsed with MART-1(27-35) peptide, and 23 of 29 specifically secreted IFN-gamma 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-gamma 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. |
