| Study Finds Immune Therapy for Metastatic Breast
Researchers at the National Cancer Institute
(NCI), one of the National Institutes of Health, have found promising
evidence that immune cell transplant therapy can help shrink tumors
in patients with metastatic breast cancer. Similar therapies, which
also involve transplantation of donated immune cells, have produced
dramatic anti-tumor effects in leukemias and lymphomas cancers
of the blood and lymph, respectively. However, previous studies
have not proven that such therapies have clinical effects on breast
Michael Bishop, M.D., NCI, led the study, which was published on
the Journal of Clinical Oncology’s website on August
16*. Scientists at the Experimental Transplantation and Immunology
Branch of NCI’s Center for Cancer Research studied 16 women
with breast cancer that had progressed to an average of three metastatic
sites after conventional treatments, including chemotherapy and
hormones; six of these had tumor shrinkage after cellular immune
Bishop’s group gave study patients a treatment similar to
a bone marrow transplant. Each patient received cells donated by
a sibling. This transplant included lymphocytes cells crucial
to the immune system and the adult stem cells that produce blood
cells. The active, anti-tumor component of this cellular immune
therapy regimen was a class of lymphocytes called T-cells, which
attack and kill tumor cells.
The same qualities that make transplanted T-cells react against
tumors especially their pugnacious tendency to attack foreign
cells also make them dangerous to the transplant recipient.
Because the recipient’s own immune system may attack donor
cells, NCI scientists gave subjects an immune-suppressing chemotherapy
regimen before the transplant. To help protect subjects’ bodies
from the toxic effects of the transplant, scientists followed the
chemotherapy with a course of transplant-conditioning drugs.
Each subject received transplants with the same concentration of
T-cells. The initial transplants had a relatively low concentration
of these cells; infusions given at 42, 70, and 98 days after the
first transplant had exponentially increasing numbers of T-cells.
Increasing the concentration over this time period helped NCI researchers
isolate patients’ reactions to the transplant from their reaction
to the chemotherapy and established T-cells as the active element
in the transplant.
Six patients of the 16 had partial or minor responses to the treatment
lasting an average of three months. The transplants had a toxic
effect in many of the women, having not only anti-tumor activity
but also attacking normal cells. This graft-versus-host disease
(GVHD) was observed in a majority of subjects: ten had acute GVHD;
of thirteen available for a follow-up examination, four had chronic
“Although it was hoped that the women would garner clinical
benefit from this research, the study was not designed to demonstrate
that this immune cell therapy results in an improvement of outcome,
specifically survival,” Bishop explained.
“The study demonstrated that immune based therapies, specifically
the lymphocyte-based therapy we used, could result in tumor regression,”
Bishop said. However, it is crucial to improve cellular immune therapy
by lowering the risk of toxic effects, especially GVHD. Collaborating
laboratories are currently testing specialized T-cells they hope
will cause little GVHD while retaining strong anti-tumor effects.
“These data provide support to continue efforts to develop
better immune-based therapies to augment currently available therapies
for metastatic breast cancer,” which is critical since current
chemotherapies for the disease result in an average survival of
only 24 months.
For more information about cancer, visit the NCI web site at http://www.cancer.gov
or call NCI’s Cancer Information Service at 1-800-4-CANCER
* Bishop, MR, Gress R. “Allogeneic Lymphocytes
Induce Tumor Regression of Advanced Metastatic Breast Cancer.”
Journal of Clinical Oncology. Vol. 22, number 19. October 1,