Lymphocyte transplant can induce regression of metastatic breast cancer

Preliminary findings suggest that a graft-versus-tumor effect against metastatic breast cancer can be achieved using allogeneic T lymphocyte grafts, according to researchers at the National Institutes of Health in Bethesda, Maryland.

While the results of an initial clinical trial testing this approach were modest, and failed to achieve a survival advantage, they provide “proof of principle” that allogeneic cellular therapy may be of benefit for this largely incurable disease, lead author Dr. Michael R. Bishop told Reuters Health.Dr. Bishop’s group enrolled 16 patients with metastatic breast cancer that had progressed despite prior chemotherapy. Each patient had an HLA-matched sibling who served as an allogeneic blood stem-cell donor. The subjects underwent a reduced-intensity conditioning regimen of cyclophosphamide and fludarabine prior to the T lymphocyte transplant.There were two partial responses (> 50% decrease in all measured lesions for at least 28 days) and four minor responses (> 25% but < 50% decrease in measured lesions), observed 42 days to 13 months posttransplantation. Median duration of response was 3 months (range 1 to 7 months), the researchers report in the October 1st issue of the Journal of Clinical Oncology.Only one response occurred without clinical evidence of graft-versus-host disease (GVHD), the authors point out. The other five patients experienced tumor progression within 2 months of starting systemic corticosteroid treatment for GVHD. After median potential follow-up of 23.4 months, median overall survival from time of transplant was 10.3 months.Dr. Bishop's team has already begun enrolling patients with metastatic breast cancer in the next trial of immunogenic therapy. But this time, "we are taking donors' lymphocytes and culturing them and actually trying to train them to cause less GVHD, yet retain their immunologic effects," Dr. Bishop said.When they tried this technique in mice that had been injected with human breast cancer cells, "we saw exactly that," he added, "that the mice developed less GVHD, yet retained a graft-versus-tumor effect."The researchers also plan to make use of complementary therapies, such as Herceptin and tamoxifen, "to first slow down the tumor rate before bringing in these immune cells to knock it down still further."Ultimately, Dr. Bishop said, "patients with extremely high-risk disease before metastases are clinically evident would be the ideal setting" for this treatment approach. "But first we have to demonstrate that this can be relatively safely administered with an acceptable toxicity profile."(Source: J Clin Oncol 2004;22:3886-3892: Reuters Health News: Karla Gale: Oncolink: October 2004.)