""""""""DISCONTINUED T cells can be activated by antigen-presenting cells. These antigen-presenting cells can provide multiple signals to activate T cells. The first signal is the interaction between the T cell receptor and a specific antigen presented in the context of an appropriate HLA class (HLA Class I for CD8+ T cells and HLA Class II for CD4+ T cells). The second signal is also usually provided by the antigen-presenting cell. One of the strongest second signals is induced by B7. We introduced the gene encoding B7 (CD28 ligand) into 3 human melanoma cell lines that are HLA-A2+ or HLA-A1+, express significant levels of LFA-3 and ICAM-1 and produce RNAs encoding the shared melanoma antigens MAGE-1 and -3, and tyrosinase. The objectives of the study are: 1) determine the maximum number of B7-transfected allogeneic melanoma cells that can be administered SQ or ID, 2) characterize the immune response to B7- transfected cells, and 3) characterize the toxicity, and 4) observe any antitumor responses. Stage IV pts. with melanoma will be typed for expression of HLA-A2 or HLA-A1. The 3 lines will be injected at 2 wk. intervals for 3 vaccinations followed by 3 injections at monthly intervals. Cohorts of pts. will receive escalating doses of 10E7 cells and 10E8 cells SQ. A final cohort will receive 10E7 cells intradermally. Twenty-eight pts. have been vaccinated. There has been 1 CR and 10 pts. with stable disease. The only toxicity has been local skin reactions. Preliminary immunologic monitoring shows that some patients have increased cytotoxic T cell lymphocyte precursors to the melanoma cell lines present in the vaccine. This study was transferred from the CRB to the MB in 1996.""""""""

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC010079-03
Application #
6163442
Study Section
Special Emphasis Panel (M)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code