BUFFALO, NY--Studies have shown that only 15% to 20% of patients with metastatic breast cancer have a long-term disease-free survival following administration of high-dose chemotherapy with autologous bone marrow or stem cell support. "We have therefore decided to explore immunotherapy for this patient population," said Meir Wetzler, MD, of the Division of Medicine, Roswell Park Cancer Institute.
Speaking at the first meeting of the Regional Cancer Center Consortium for Biological Therapy of Cancer, hosted by Roswell Park Cancer Institute, Dr. Wetzler described several possible immunotherapy approaches.
One approach would be to use an immune modulator such as interleukin-2 (IL-2) or granulocyte-macrophage colony stimulating factor (GM-CSF). An initial study of five patients treated with
IL-2 (10 days of low-dose therapy, 3 days of intermediate-dose therapy, and 1 day of rest, repeated six times) after autologous transplantation showed a 30- to 40-fold increase in the natural killer cell population without any significant change in total white blood cell counts.
The treatment was well tolerated, with only one patient needing a short hospitalization due to development of orthostatic hypotension.
Another approach, adoptive immunotherapy, currently being developed at Roswell Park in the laboratory of Elizabeth Repasky, PhD, will use more specific targets such as breast cancer peptides (for example, the HER-2/neu peptide) or CEA-vaccinia vaccine, to induce antitumor-specific T cells. These agents will be administered to patients following high-dose chemotherapy. Their T cells will then be collected and re-infused following transplantation.
"However, one of the caveats in this approach is that we do not know enough about the ability of these patients to mount an immune response following high-dose chemotherapy," Dr. Wetzler said. A study has been initiated at Roswell Park to analyze the delayed-type immune response of these patients before and after high-dose chemotherapy.
Specific Immune Responses
Finally, patients with metastatic breast cancer who are without any evidence of disease more than 1 year following high-dose chemotherapy/autologous transplantation may have developed a specific immune response to their disease.
"We propose to collect their T cells and analyze them for specific clones that will either react with known breast peptides or allow us to identify new antigens," Dr. Wetzler said. "We are looking for potential collaborators for these studies," he added.