Researchers at the National Cancer Institute (NCI), one of the National Institutes of Health, have found promising evidence that immune cell transplant therapy can help shrink tumors in patients with metastatic breast cancer. Similar therapies, which also involve transplantation of donated immune cells, have produced dramatic anti-tumor effects in leukemias and lymphomas--cancers of the blood and lymph, respectively. However, previous studies have not proven that such therapies have clinical effects on breast cancer.
Michael Bishop, M.D., of NCI, led the study, which was published on August 16 on the Web site of the Journal of Clinical Oncology.* Scientists at the Experimental Transplantation and Immunology Branch of NCI's Center for Cancer Research studied 16 women with breast cancer that had progressed to an average of three metastatic sites after conventional treatments, including chemotherapy and hormones; six of these women had tumor shrinkage after cellular immune therapy.
Bishop's group gave study patients a treatment similar to a bone marrow transplant. Each patient received cells donated by a sibling. This transplant included lymphocytes -- cells crucial to the immune system -- and the adult stem cells that produce blood cells. The active, anti-tumor component of this cellular immune therapy regimen was a class of lymphocytes called T cells, which attack and kill tumor cells.
The same qualities that make transplanted T cells react against tumors --especially their pugnacious tendency to attack foreign cells -- also make them dangerous to the transplant recipient. Because the recipient's own immune system may attack donor cells, NCI scientists gave subjects an immune-suppressing chemotherapy regimen before the transplant. To help protect subjects' bodies from the toxic effects of the transplant, scientists followed the chemotherapy with a course of transplant-conditioning drugs.
Each subject received transplants with the same concentration of T cells. The initial transplants had a relatively low concentration of these cells; infusions given at 42, 70, and 98 days after the first transplant had exponentially increasing numbers of T cells. Increasing the concentration over this time period helped NCI researchers isolate patients' reactions to the transplant from their reaction to the chemotherapy, and established T cells as the active element in the transplant.
Six patients of the 16 had partial or minor responses to the treatment lasting an average of three months. The transplants had a toxic effect in many of the women, causing not only anti-tumor activity but also attacking normal cells. This graft-vs.-host disease (GVHD) was observed in a majority of subjects: 10 had acute GVHD; of 13 available for a follow-up examination, four had chronic GVHD.
"Although it was hoped that the women would garner clinical benefit from this research, the study was not designed to demonstrate that this immune cell therapy results in an improvement of outcome, specifically survival," Bishop explained.
"The study demonstrated that immune-based therapies, specifically the lymphocyte-based therapy we used, could result in tumor regression," Bishop said. However, it is crucial to improve cellular immune therapy by lowering the risk of toxic effects, especially GVHD. Collaborating laboratories are currently testing specialized T cells they hope will cause little GVHD while retaining strong anti-tumor effects.
"These data provide support to continue efforts to develop better immune-based therapies to augment currently available therapies for metastatic breast cancer," stated Bishop. Such advancement is critical, as current chemotherapies for the disease result in an average survival of only 24 months.
* Bishop, MR, Gress R. "Allogeneic Lymphocytes Induce Tumor Regression of Advanced Metastatic Breast Cancer." Journal of Clinical Oncology. Vol. 22, number 19. October 1, 2004.
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