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NEW GENE-BASED TREATMENT APPROACHES

By Sean Henahan, Access Excellence


LOS ANGELES- 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, PA.

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.


Further cancer information online

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