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New Method Of Gene Therapy Offers Hope For Treatment Of Melanoma, Other Common Cancers

Date:
September 1, 2006
Source:
NIH, National Cancer Institute
Summary:
Scientists have demonstrated sustained regression of advanced melanoma in a study of 17 patients by genetically engineering patients' own white blood cells to recognize and attack cancer cells.

A team of researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, has demonstrated sustained regression of advanced melanoma in a study of 17 patients by genetically engineering patients' own white blood cells to recognize and attack cancer cells. The study appears in the online edition of the journal Science on August 31, 2006*.

"These results represent the first time gene therapy has been used successfully to treat cancer. Moreover, we hope it will be applicable not only to melanoma, but also for a broad range of common cancers, such as breast and lung cancer," said NIH Director Elias A. Zerhouni, M.D.

Autologous lymphocytes -- a person's own white blood cells -- have previously been used to treat metastatic melanoma. In a process called adoptive cell transfer, lymphocytes are first removed from patients with advanced melanoma. Next, the most aggressive tumor-killing cells are isolated, multiplied in the lab, and then reintroduced to patients who have been depleted of all remaining lymphocytes. While reasonably successful, this method can only be used for melanoma patients and only for those who already have a population of specialized lymphocytes that recognize tumors as abnormal cells.

Thus, NCI researchers, led by Steven A. Rosenberg, M.D., Ph.D., sought an effective way to convert normal lymphocytes in the lab into cancer-fighting cells. To do this, they drew a small sample of blood that contained normal lymphocytes from individual patients and infected the cells with a retrovirus in the laboratory. The retrovirus acts like a carrier pigeon to deliver genes that encode specific proteins, called T cell receptors (TCRs), into cells. When the genes are turned on, TCRs are made and these receptor proteins decorate the outer surface of the lymphocytes. The TCRs act as homing devices in that they recognize and bind to certain molecules found on the surface of tumor cells. The TCRs then activate the lymphocytes to destroy the cancer cells.

In this study, newly engineered lymphocytes were infused into 17 patients with advanced metastatic melanoma. There were three groups of patients in this study. The first group consisted of three patients who showed no delay in the progression of their disease. As the study evolved, the researchers improved the treatment of lymphocytes in the lab so that the cells could be administered in their most active growth phase. In the remaining two groups, patients received the improved treatments. Two patients experienced cancer regression, had sustained high levels of genetically altered lymphocytes, and remained disease-free over one year. One month after receiving gene therapy, all patients in the last two groups still had 9 percent to 56 percent of their TCR-expressing lymphocytes. There were no toxic side effects attributed to the genetically modified cells in any patient.

Approaches to increase the function of the engineered TCRs -- including the development of TCRs that can bind to tumor cells more tightly -- and to further optimize delivery methods using retroviruses are under investigation. In addition, the researchers believe it may be beneficial to further modify lymphocytes by inserting molecules that assist in directing lymphocytes to cancerous tissues. Clinical trials are being conducted to enhance treatment effectiveness using total body radiation therapy to deplete a patient's supply of non-altered lymphocytes before replacing them with purely engineered cells. The researchers also have isolated TCRs that recognize common cancers other than melanoma.

"We are currently treating advanced melanoma patients using adoptive transfer of genetically altered lymphocytes, and we have now expressed other lymphocyte receptors that recognize breast, lung, and other cancers," said Rosenberg.

"These very exciting successes in treating advanced melanoma bring hope that this type of gene therapy, altering lymphocytes, could be used in many types of common cancers and could be achievable in the near future," said Acting NCI Director John E. Niederhuber, M.D. He acknowledged Rosenberg for his persistent and visionary study of the role of the immune system in the treatment of cancer. "He is one of the leaders we all look to for moving us forward," Niederhuber said.

Skin cancer is the most common of all cancers. According to the American Cancer Society, melanoma accounts for about 4 percent of skin cancer cases, but it is also the most serious and most aggressive type. In the United States, an estimated 62,190 new cases of melanoma will be diagnosed and approximately 7,910 people will die of the disease in 2006.

* Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients mediated by transfer of genetically engineered lymphocytes. Science Express. Online August 31, 2006.


Story Source:

The above story is based on materials provided by NIH, National Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

NIH, National Cancer Institute. "New Method Of Gene Therapy Offers Hope For Treatment Of Melanoma, Other Common Cancers." ScienceDaily. ScienceDaily, 1 September 2006. <www.sciencedaily.com/releases/2006/09/060901112104.htm>.
NIH, National Cancer Institute. (2006, September 1). New Method Of Gene Therapy Offers Hope For Treatment Of Melanoma, Other Common Cancers. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2006/09/060901112104.htm
NIH, National Cancer Institute. "New Method Of Gene Therapy Offers Hope For Treatment Of Melanoma, Other Common Cancers." ScienceDaily. www.sciencedaily.com/releases/2006/09/060901112104.htm (accessed October 21, 2014).

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