Early trials using targeted monoclonal antibodies in combination with existing therapies show promise in treating metastatic breast cancer, according to research presented by investigators from the University of Pennsylvania's Abramson Cancer Center at the 2010 meeting of the American Society of Clinical Oncology.

The investigators used an antibody previously approved by the FDA to enhance the effectiveness of a therapeutic vaccine for women with advanced breast cancers. The antibody, known as anti-CD25 mAb dacluzimab, targets T regulatory cells (Tregs), naturally occurring cells which tumors harness to dampen the body's normal immune response. Until now, these cells have represented an obstacle to cancer immunotherapy. The Penn Medicine team's approach uses the antibody to turn off the Treg cells' function in the immune system and boosting the effectiveness of a telomerase/survivin peptide vaccine made to tackle the cancer.

The study demonstrated that a single infusion of the antibody given a week before patients received the vaccine results in "rapid, marked and prolonged" loss of Tregs without toxicity in patients with metastatic breast cancer. Six of the 10 patients who received the treatment exhibited a stabilization of their disease. Data for overall survival is not yet available, but the Penn researchers say the results represent significant promise for treating the patient population that does not respond to standard therapies.

"Many of these women have already been treated with and failed several chemotherapy regimens, but using this approach they were able to receive multiple doses of the vaccine without experiencing any of the toxicities that often accompany chemotherapy," says senior author Robert H. Vonderheide, MD, DPhil, an associate professor in the division of Hematology/Oncology. "For this group of patients, an extended period of stable disease represents an encouraging result." He and his team plan to begin much larger studies in the near future, and ultimately, to expand the new combined approach to women who are currently in remission but at very high risk of relapse.

Tregs play an important role in the body's normal immune response. When they are absent or severely depleted, the result is autoimmune problems. To date, however, research has not shown any long-term effects of this targeted immune suppression in the treated patients, which is an important consideration in expanding the trials to women without known active disease.

"Ten years ago, we didn't even know Tregs existed," Vonderheide says. "Our lack of knowledge about the intricacies of the normal immune system and the ways in which tumors can exploit the immune response severely limited the success of previous attempts at cancer immunotherapy. The early results were quite modest and very transient. It has taken five years to develop an understanding of how these cells work, but we have now reached the point where we are on the cusp of a whole new era in cancer immunotherapy."

SOURCES:
Annual Meeting of the American Society of Clinical Oncology, June 8, 2010, Chicago, IL
University of Pennsylvania School of Medicine (http://www.uphs.upenn.edu)