News and Research
Immune System
New Approach To Replacing Immune Cells Shrink Tumors In
Patients With Melanoma
9-20-2002
A new approach to cancer treatment that replaces a patient's
immune system with cancer-fighting cells can lead to tumor
shrinkage, researchers report today in the journal Science.
The study demonstrates that immune cells, activated in the
laboratory against patients' tumors and then administered
to those patients, can attack cancer cells in the body.
The
experimental technique, known as adoptive transfer, has
shown promising results in patients with metastatic melanoma
who have not responded to standard treatment. With further
research, scientists hope this approach may have applications
to many cancer types, as well as infectious diseases such
as AIDS.
In
the study, 13 patients with metastatic melanoma (a deadly
form of skin cancer) who had not responded to standard treatments
were treated with immune cells produced in the laboratory
specifically to destroy their tumors. The treatment resulted
in at least 50 percent tumor shrinkage in six of the patients,
with no growth 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, the lead researcher on the
study.
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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.
The adoptive transfer technique fights cancer with
T cells, immune cells that recognize and kill foreign cells that have
invaded the body. Researchers used a small fragment of each patient's
melanoma tumor to grow T cells in the laboratory, using T cells originally
taken from the patients. Exposure to the tumor activated the immune
cells so that they would recognize and attack cells from each specific
cancer.
Once the T cells had multiplied to a sufficient number
to be used for treatment, they were administered to patients. Patients
were also given a high dose of a protein called interleukin-2 (IL-2),
which stimulates continued T cell growth in the body. Prior to the
immunotherapy, chemotherapy had been used to deplete patients' own
immune cells, which had proven ineffective at fighting the cancer.
Diminishing the old cells provided an opportunity for the new T cells
to repopulate patients' immune systems. 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 patients' immune systems. They persisted
for several months and were able to destroy metastases throughout
the body.
Over time, patients' old immune systems recovered,
restoring their ability to fight infections. Researchers report that
among the patients in the study, only occasional opportunistic infections
developed during treatment.
Other side effects were mild autoimmune disorders.
T cells act by recognizing a protein fragment called an antigen on
the outside of the tumor cells. Antigens found on tumor cells may
also be found on certain normal cells in the body, making them vulnerable
to attack. Autoimmune effects among the patients in the study were
mild and easily controlled.
Although the treatment is highly experimental, researchers
are optimistic that it may, in the future, extend beyond the treatment
of patients with melanoma. It should be possible, they say, to raise
immune cells that will recognize and attack many tumor types.
Similarly, the same technique could potentially be
used to treat some infectious diseases, such as AIDS.
This
article has been adapted from a news release issued by NIH/National
Cancer Institute, www.nci.nih.gov.
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