Donor immune cells attack metastatic breast cancer

In patients with metastatic breast cancer, immune cells from a genetically matched donor can attack and shrink tumors, researchers from the National Cancer Institute (NCI) announced today at the Annual Meeting of the American Society of Clinical Oncology in Chicago. This is the first time researchers have clearly demonstrated this type of immune response, known as a graft-versus-tumor effect, acting against breast cancer.

“Graft-versus-tumor effects have been shown to be useful in treating cancers of the blood, such as leukemia and lymphoma. Breast cancer, however, has generally been resistant to immune-based therapies,” said Michael Bishop, M.D., of NCI’s Center for Cancer Research, the lead author on the study. “Although the tumors of patients in this study were not completely eliminated by the treatment, the responses we saw provide hope that immunotherapies for breast cancer are worth pursuing.”

Tumor regression has been observed in the past in some patients with metastatic breast cancer who received stem cell transplants, but it was unclear whether immune cells had attacked the tumor or the tumor was shrinking in response to chemotherapy drugs administered prior to the transplant. The design of this clinical trial, however, allowed researchers to attribute tumor regression to a true graft-versus-tumor effect.

Each of the 13 patients in the Phase I trial had received multiple previous treatments for metastatic breast cancer. In the study, patients first received conventional doses of chemotherapy to kill cancer cells and reduce the cells in their immune system so that donor cells could replace them. They then received stem cells from the blood of HLA-matched siblings. HLA-matched donor cells, which have the same set of proteins (known as human leukocyte-associated antigens) on their surface as the patient’s own cells, are much more likely to be accepted by the patient’s body.

T cells, specialized immune cells that recognize and kill foreign cells that have invaded the body, were removed from the pool of donated stem cells prior to transplant. These T cells were given to patients later, in an initial infusion 42 days after stem cell transplant, then in two follow-up infusions over the next two months. Because T cells were not given immediately following chemotherapy, researchers were able to attribute any tumor cell death to the transplanted T cells rather than to anti-tumor effects of the chemotherapy drugs.

In four patients, tumors shrunk at least 50 percent in response to the treatment. A minor response was seen in three of the other patients. Although not all patients in the study responded to treatment, and none of the tumors was eliminated entirely, the results of the trial provide evidence that transplanted T cells can attack tumors in patients with metastatic breast cancer. Researchers are optimistic that further study could lead to effective immunotherapies for these patients.

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