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Senior Citizen Health & Medicine
Researchers Find Success in Engineering White Blood
Cells to Kill Cancer Cells
New method of gene therapy developed at National
Cancer Institute
 August 31, 2006 Scientist at the National Cancer
Institute are finding success in treating cancer with gene therapy,
hoping to find a more effective treatment than chemotherapy or
radiation. They have recently found success in melanoma patients by
engineering the patient's own white blood cells to recognize and attack
the cancer cells. This success, they hope, will lead to treating a
number of common cancers.
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Health & Medicine |
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These results represent the first time gene
therapy has been used successfully to treat cancer. Moreover, we hope it
will be applicable not only to melanoma, but also for a broad range of
common cancers, such as breast and lung cancer, said National
Institutes of Health Director Elias A. Zerhouni, M.D.
Autologous lymphocytes a persons own white blood
cells have previously been used to treat metastatic melanoma. In a
process called adoptive cell transfer, lymphocytes are first removed
from patients with advanced melanoma.
Next, the most aggressive tumor-killing cells are
isolated, multiplied in the lab, and then reintroduced to patients who
have been depleted of all remaining lymphocytes. While reasonably
successful, this method can only be used for melanoma patients and only
for those who already have a population of specialized lymphocytes that
recognize tumors as abnormal cells.
Thus, NCI researchers, led by Steven A. Rosenberg,
M.D., Ph.D., sought an effective way to convert normal lymphocytes in
the lab into cancer-fighting cells. To do this, they drew a small sample
of blood that contained normal lymphocytes from individual patients and
infected the cells with a retrovirus in the laboratory. The retrovirus
acts like a carrier pigeon to deliver genes that encode specific
proteins, called T cell receptors (TCRs), into cells.
When the genes are turned on, TCRs are made and
these receptor proteins decorate the outer surface of the lymphocytes.
The TCRs act as homing devices in that they recognize and bind to
certain molecules found on the surface of tumor cells. The TCRs then
activate the lymphocytes to destroy the cancer cells.
In this study, newly engineered lymphocytes were
infused into 17 patients with advanced metastatic melanoma. There were
three groups of patients in this study. The first group consisted of
three patients who showed no delay in the progression of their disease.
As the study evolved, the researchers improved the treatment of
lymphocytes in the lab so that the cells could be administered in their
most active growth phase. In the remaining two groups, patients received
the improved treatments.
Two patients experienced cancer regression, had
sustained high levels of genetically altered lymphocytes, and remained
disease-free over one year. One month after receiving gene therapy, all
patients in the last two groups still had 9 percent to 56 percent of
their TCR-expressing lymphocytes. There were no toxic side effects
attributed to the genetically modified cells in any patient.
Approaches to increase the function of the
engineered TCRs including the development of TCRs that can bind to
tumor cells more tightly and to further optimize delivery methods
using retroviruses are under investigation.
In addition, the researchers believe it may be
beneficial to further modify lymphocytes by inserting molecules that
assist in directing lymphocytes to cancerous tissues. Clinical trials
are being conducted to enhance treatment effectiveness using total body
radiation therapy to deplete a patients supply of non-altered
lymphocytes before replacing them with purely engineered cells.
The researchers also have isolated TCRs that
recognize common cancers other than melanoma.
We are currently treating advanced melanoma
patients using adoptive transfer of genetically altered lymphocytes, and
we have now expressed other lymphocyte receptors that recognize breast,
lung, and other cancers, said Rosenberg.
These very exciting successes in treating advanced
melanoma bring hope that this type of gene therapy, altering
lymphocytes, could be used in many types of common cancers and could be
achievable in the near future, said NCI Director John E. Niederhuber,
M.D.
Niederhuber acknowledged Rosenberg for his
persistent and visionary study of the role of the immune system in the
treatment of cancer. He is one of the leaders we all look to for moving
us forward, he said.
Skin cancer is the most common of all cancers.
According to the American Cancer Society, melanoma accounts for about 4
percent of skin cancer cases, but it is also the most serious and most
aggressive type. In the United States, an estimated 62,190 new cases of
melanoma will be diagnosed and approximately 7,910 people will die of
the disease in 2006.
The study appears in the online edition of the
journal Science on August 31, 2006.
For a Q&A on gene therapy techniques similar to
those used in this study, go to:
http://www.cancer.gov/cancertopics/factsheet/Therapy/gene.
For more information on Dr. Rosenbergs research,
go to
http://ccr.cancer.gov/staff/staff.asp?profileid=5757.
For more information about cancer, please visit the
NCI Web site at
http://www.cancer.gov, or call NCI's Cancer Information Service at
1-800-4-CANCER (1-800-422-6237).
The National Institutes of Health (NIH) The
Nation's Medical Research Agency - includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic,
clinical and translational medical research, and it investigates the
causes, treatments, and cures for both common and rare diseases. For
more information about NIH and its programs, visit
www.nih.gov.
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