NEW GENE-BASED TREATMENT APPROACHES
By Sean Henahan, Access Excellence
Gene therapy, immune system modulation and
genetically engineered antibodies are all promising fronts in the
war against cancer, reported researchers at the annual meeting of
the American Society of Clinical Oncology.
Current approaches to the treatment of cancer involve
killing cancer cells with toxic chemicals, radiation or surgery.
Several new biological and gene based therapies aim instead to
enhance the body's natural defenses against invading cancers.
In the first study of its kind, researchers evaluated the
ability of genetically engineered DNA to shrink tumors in
humans. Allovectin-7, the genetic material that makes a
transplantation antigen protein called HLA-B7, was injected
directly into the tumors of more than 40 patients. The early
results showed that the injections increased the ability of the
immune system to recognize the cells as cancer cells, and to
destroy them. Improvements were seen in a number of tumor types,
including melanoma, renal cell carcinoma and colon cancer,
reported Dr. Gary Nabel, University of Michigan..
"These data represent for the first time gene therapy
approaches have been tried in cancer patients. Gene therapy
represents an exciting way to increase the body's ability to
recognize and shrink cancer cells. What's exciting about these
studies is that they demonstrate our increasingly sophisticated
understanding of what causes a cell to become cancerous, as well
as our ability to interfere with the process," said Dr. Lynn Mara
Schucter, University of Pennsylvania Cancer Center, Philadelphia,
Researchers at the Columbia-Presbyterian Medical Center in
New York presented promising data from a different kind of gene
therapy. Peripheral blood stem cells (PBSTs) are critical for
helping patients recover from the debilitating effects of
chemotherapy. Unfortunately, these cells are often destroyed by
toxic drug regimens, impairing the success of bone marrow
transplantation. The Columbia researchers successfully made the
PBST's resistant to the toxic effects of chemotherapy by
transferring resistance genes into them.
The transfer of resistance genes into PBST's has the
potential to enable patients with advanced cancers to undergo
more intensive chemotherapy without the toxicity to the bone
marrow that normally accompanies such treatment.
Researchers have been attempting to develop tumor specific
antibodies for many years. While many antibodies have been
developed, problems have included immunogenicity, poor
specificity and insufficient uptake binding to cancer cells. A
group of researchers from Sloan-Kettering Cancer Center in new
York appear to have made an important breakthrough in this area.
Dr. Jose Baselga and colleagues developed a recombinant
humanized monoclonal antibody, rhuMAb HER2, that binds
specifically to growth factor receptors on cancer cells. Once it
binds to the cells, they can no longer keep growing. High levels
of HER2 oncogene, the gene product targeted by the monoclonal,
are found in breast cancer and other tumors.
The early results of a clinical trial with the monoclonal
appeared promising with one complete remission of tumor and
several cases of significant tumor shrinkage. Another important
observation was that patient were able to tolerate the antibody
for as long as two years with developing immunogenic responses, a
problem seen with previous monoclonal antibody candidates.
In another study, Italian researchers reported that adding
recombinant interferon to standard surgical therapy greatly
improved survival rates in patients with one of the fastest
growing types of cancers, malignant melanoma. Survival rates were
20% higher in patients who received interferon therapy after
surgery, compared with patients who received surgery alone.
For more information on the studies cited in this article
see the May 1995 issue of The Journal of Clinical Oncology.
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