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 | $1,602,394 | Project Dates | 00/00/0000 - 00/00/0000 |
Fiscal Year | 2013 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Childhood Cancers (3.0%) Cancer (100.0%) Cancer Survivorship (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%) |
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Research Type | |||
Systemic Therapies - Discovery and Development | |||
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, MAGE-A3, and CEA epitopes. Chimeric antigen receptors have been developed that recognize CD19 cell surface antigens on B cell malignancies and the EGFRvIII mutation expressed on glioblastomas. Clinical trials are being performed to study the treatment of patients with a variety of cancer types using these transduced cells. Multiple patients treated with cells transduced with a chimeric receptor targeting CD19 have had substantial responses. 80% of patients treated have had objective responses in the absence of IL-2 administration. Using cells transduced with a TCR reactive with the NY-ESO-1 cancer testes antigen 10 of 19 melanoma patients and 10 of 15 synovial cell sarcoma patients have had objective responses. |