Steps made toward overcoming biological obstacles to cell therapy for cancer

Certain types of white blood cells assist the body in destroying cancerous tumors. Among these are CD8+ T cells. The T is for thymus, the gland near the base of the throat that both raises up and weeds out blood cells involved in immune responses.

One of the strategies being explored to eradicate established tumors is to increase the number of tumor-reactive T cells through immunization (often called a "cancer vaccine") or by growing large numbers of the patient's tumor-reactive T cells outside the body and giving them back to the patient, a method called adoptive immunotherapy.

CD8+T cells detect proteins called antigens and respond in fighting mode. If such antigens are detected on tumor cells, the CD8+ T cells punch holes in the tumor cells and destroy their contents. However, many tumor antigens are also found in normal body tissues. As a result, the thymus must get rid of most of the tumor-reactive T cells to keep the body from attacking itself.

"Those CD8+ T cells that can recognize such tumor antigens but evade thymic deletion are potentially harmful, and thus are held in check inside the body by mechanisms that make them tolerant of the protein even if it is encountered on a tumor cell," said Dr. Philip Greenberg, University of Washington (UW) professor of medicine and immunology, one of the co-authors of a Feb. 13, 2006, paper in Nature Medicine on new research in adoptive immunotherapy.

However, at times the system operates too well. Because tumor cells express higher levels of many of these antigens than do normal cells, some T cells can recognize the tumor cells and largely ignore the normal cells, but these CD8+ T cells are also held in check inside the body by mechanisms that build up their tolerance to the presence of tumor antigens. They become deficient in sending the signals that lead to tumor-cell killing.

"It is precisely these cells that might be most effective in tumor therapy, albeit with some potenti

Contact: Leila Gray
University of Washington

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