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 cancer.
Michael Bishop, M.D., NCI, led the study, which was
published on the ‘Journal of Clinical Oncology’s’ website. 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 therapy.
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
GVHD.
“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.