New Approach to Replacing Immune Cells Shrinks Tumors in Patients with Posted Thursday, September 19, 2002 by ctustis
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.

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.

* Dudley ME, et al. Cancer regression and autoimmunity following clonal
repopulation with anti-tumor lymphocytes and non-myeloablative
conditioning. Published online on Science Express,
http://www.sciencemag.org/sciencexpress/recent.shtml, Sept. 19,2002.
Source: http://newscenter.cancer.gov/pressreleases/melanomavaccine.html