New approach to immunotherapy shows promise against advanced melanoma
Adoptive transfer, a new technique in which
large numbers of a patient's T cells--- activated to attack the patient's
individual tumor--- has shown great promise against advanced melanoma,
according to an article in the September 19th online publication of
Science.
Researchers at the National Cancer Institute
exposed T cells to tumor samples, stimulated cell division, and
then transfused a large number of T cells back into the patient
after chemotherapy had depleted the supply of inactive cells.
In the study, 13 patients with metastatic
melanoma that had not responded to standard treatments were treated
with immune cells produced specifically to destroy their tumors.
The treatment resulted in at least 50 percent tumor shrinkage in
six of the patients, with no growth of tumors or appearance of new
tumors. Four additional patients had some cancer growths disappear.
Researchers have tried previously to treat
cancer with immune cells but the cells did not survive well in the
body. "In the past, only a fraction of a percent of the cells
we injected were able to survive, and they would persist for only
a few days," said Steven A. Rosenberg, M.D., Ph.D., of the
National Cancer Institute, a researcher on the study.
Improvements in the way immune cells are generated
in the laboratory and the way patients' bodies are prepared to receive
them, however, have led to dramatically different results. "We
have been able to generate a very large number of immune cells that
appear in the blood and constitute a majority of the immune system
of the patient. These persist for over four months and are able
to attack the tumor," Rosenberg said.
With the adoptive transfer technique, researchers
used a small fragment of each patient's melanoma tumor to activate
some of the patient's T cells. After the cells had multiplied to
a sufficient number, they were administered to the patient. Each
patient was also given a high dose of interleukin-2 to stimulate
continued T-cell division in the body. Prior to the infusion, chemotherapy
was used to deplete the patients' inactive immune cells and provide
an opportunity for the new T cells to repopulate the immune system.
Analysis of blood and tumor samples from many
of the patients who responded favorably to the treatment revealed
that the administered immune cells were thriving, multiplying rapidly,
and attacking tumor tissue. T cells activated against melanoma became
the major component in these patients' immune systems. They persisted
for several months and were able to destroy metastases throughout
the body.
Over time, patients' endogenous immune systems
recovered, restoring full ability to fight infections. Researchers
report that among the patients in the study, only occasional opportunistic
infections developed during immunotherapy. Other side effects were
mild autoimmune disorders. Autoimmune effects were mild and easily
controlled.
Although the treatment is highly experimental,
researchers are optimistic that it may, in the future, be useful
for many tumor types. Similarly, the same technique could potentially
be used to treat some infectious diseases such as AIDS.
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