Sibling-donated T-cells produced partial responses in some women with metastatic breast cancer, suggesting that immune therapy may hold promise for these patients, according to an article published online August 16th by the Journal of Clinical Oncology.

Similar therapies, which also involve transplantation of donated immune cells, have produced dramatic anti-tumor effects in leukemias and lymphomas. However, previous studies have not proven that such therapies have clinical effects on breast cancer.

Michael Bishop, MD, and colleagues at the National Cancer Institute studied 16 women with breast cancer that had progressed to an average of three metastatic sites after conventional treatments including chemotherapy and hormones. Of the 16 patients, 6 (38 percent) had tumor shrinkage after cellular immune therapy.

In the trial, each patient received T-cells donated by a sibling. The transplant included both the lymphocytes and adult stem cells. To avoid immune attack by the recipient’s system, the researchers 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 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 time helped researchers isolate patients' reactions to the transplant from their reaction to the chemotherapy and established T- cells as the active element in the transplant.

Of the 16 patients, 6 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, having not only anti-tumor activity but also attacking normal cells. This graft-versus-host disease (GVHD) was observed in a majority of subjects: 10 women had acute GVHD; of 13 women available for a follow-up examination, 4 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," which is critical since current chemotherapies for the disease result in an average survival of only 24 months.