ZIA BC 010985 (ZIA) | |||
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Title | Gene therapy of cancer | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Rosenberg, Steven | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $1,264,583 | Project Dates | 10/01/2008 - N/A |
Fiscal Year | 2009 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Cancer Survivorship (3.0%) Childhood Cancers (3.0%) Digestive Diseases (10.0%) Gene Therapy (40.0%) Gene Therapy Clinical Trials (40.0%) |
Colon/Rectum (10.0%) Melanoma (80.0%) Sarcoma (10.0%) Sarcoma, Soft (Sarcoma Subset) (10.0%) |
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Research Type | |||
Systemic Therapies - Discovery and Development Systemic Therapies - Clinical Applications |
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Abstract | |||
My laboratory is involved in studies to genetically modify autologous lymphocytes to improve their anti-tumor activity. In 1990 we reported the first studies of gene transfer in humans which involved the adoptive transfer of TIL transduced with a marker gene encoding neomycin phosphotransferase. These studies suggested the possibility that genes could be inserted into lymphocytes to improve their anti-tumor efficacy. We have now made progress in this area by developing techniques for the high efficiency transduction of human lymphocytes. The genes encoding high affinity anti-tumor T cell receptors (TCR) that recognize antigens on melanomas and common epithelial cancers have been identified and clinical trials to use autologous T cells transduced with these TCRs have begun. In recent studies we have shown that up to 30% of patients with metastatic melanoma will achieve objective clinical cancer regressions when treated with their autologous lymphocytes that have been transduced with T cell receptors that recognized the MART-1 or gp100 melanoma antigens. T cell receptors have now been identified that recognize NY-ESO-1, p53, and CEA epitopes. C+himeric antigen receptors have been developed that recognize the HER-2 cell surface antigen. Clinical trials will be performed to study the treatment of patients with common epithelial malignancies using these transduced cells. |