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
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
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.