الثلاثاء، 1 فبراير 2011

NIH researchers extend use of gene therapy to treat a soft tissue tumor

NIH researchers extend use of gene therapy to treat a soft tissue tumor
Results of an intermediate stage clinical trial of several dozen people provides evidence that a method that has worked for treating patients with metastatic melanoma can also work for patients with metastatic synovial cell sarcoma, one of the most common soft tissue tumors in adolescents and young adults. This study is the first to use genetically modified immune cells, in a technique known as adoptive therapy, to cause cancer regression in patients with a solid cancer as opposed to melanoma. This approach represents a method for obtaining immune cells from any cancer patient and converting them into ones that can recognize cancer cells expressing the target antigen, NY-ESO-1, according to researchers at the National Cancer Institute. The study appeared in the Jan. 31, 2011, issue of the Journal of Clinical Oncology.
NY-ESO-1 is a protein found in up to 50 percent of melanomas and cancers of the breast, prostate, esophagus, lung, and ovary, and in 80 percent of synovial sarcomas. "Since NY-ESO-1 is expressed in a substantial number of cancers, beside melanoma and synovial sarcoma, it is an attractive target for immune-based therapies against these cancers as well," said lead investigator Steven Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI’s Center for Cancer Research.
The CAT scans of a patient with synovial cell sarcoma, taken pre-treatment and at 14 months, show a dramatic response of lung metastases to treatment with the NY-ESO-1 gene-engineered cells.
This work builds upon previously published results in patients with metastatic melanoma. Those studies showed that metastatic melanoma patients could be treated by infusion with their own genetically modified T cells, or white blood cells, that had receptors on their surfaces that recognized an antigen on the melanoma cells.
In this study, 17 patients with synovial cell sarcoma or metastatic melanoma, whose tumors expressed NY-ESO-1, received therapy with their own immune cells engineered to express a T cell receptor capable of recognizing the NY-ESO-1 antigen. To perform this treatment, the investigators isolated normal white blood cells, called lymphocytes, from each patient’s blood and modified these cells by inserting the gene encoding the anti-tumor T cell receptor into them. These genetically modified cells were then able to recognize and destroy NY-ESO-1-expressing cancer cells. The results showed tumor regression in four of the six patients with synovial cell sarcoma and in five of the 11 melanoma patients. A partial response that lasted 18 months was observed in one of the synovial cell sarcoma patients, while two of the melanoma patients demonstrated complete ongoing regression responses that lasted 20 months or longer, which for patients with these diseases, is significant.
"Now that we have shown that a patient’s own cells genetically engineered to express a receptor against the NY-ESO-1 antigen can mediate tumor regression, we will be optimizing this treatment and extending it to the treatment of patients with other common cancers," said Rosenberg.
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Reference: Robbins PF, et al., Tumor regression in patients with metastatic synovial sarcoma and melanoma using engineered lymphocytes reactive with NY-ESO-1, Journal of Clinical Oncology, DOI: 10.1200/JCO.2010.32.2537, January 31, 2011.
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