Researchers at Mount Sinai School of Medicine began clinical trials on a unique and promising approach to gene therapy for colorectal cancer. The study uses genes to make the cancer cells look foreign to the body's immune system, which will then attack and destroy the cancer.
Colorectal cancer is the second leading cancer killer in the United States. The American Cancer Society estimates that 147,500 cases of colorectal cancer will be diagnosed in the country in 2003 and 57,000 people will die from the disease.
In experiments with laboratory animals, Mount Sinai researchers have demonstrated that their approach to gene therapy, known as tumor immunization, extended life in all animals tested and wiped out cancer entirely in up to 20% of animals whose cancer had spread from the colon to the liver.
"Cancer cells are able to grow unimpeded by the body's defenses because they look very similar to healthy cells, with only very subtle differences that pass under the radar screen of the body's immune cells," said Savio Woo, PhD, Director of the Carl C. Icahn Center for Gene Therapy and Molecular Medicine at Mount Sinai School of Medicine. "We use gene transfer technology to insert a gene into the cancer cells that makes them visible to the body's natural immune defenses."
The method of tumor immunization which Mount Sinai researchers developed involves transferring a gene that codes for Interleukin-12 (IL12) into cancer cells directly in the patient's tumor. IL12 is a protein that is not normally produced by cancer cells. When the cancer cells produce this protein as a result of gene transfer it acts as a signal to a special class of white blood cells of the immune system telling them, "These cancer cells are dangerous. Come over here and destroy them."
The laboratory and animal studies conducted by Dr. Woo and colleagues have provided evidence that delivering the IL12 gene to cancer cells can trigger a targeted immune response that destroys tumor cells. Their impressive results along with extensive pharmacological and toxicology studies they conducted were sufficient evidence to convince the FDA, NIH and Mount Sinai's Institutional Review Board that the promise of this research is ready to be tested in humans. The first phase of a clinical trial to establish the safety of these treatments in humans began recently.
Dr. Woo and colleagues developed a virus that can carry the IL12 gene into the cancer cells. "The virus is developed in a special multi-million dollar facility here at Mount Sinai," said Dr. Woo. "This state-of-the-art facility provides us the means to produce an engineered virus so that it can not reproduce itself and can not lead to a sustained infection in patients. In animal experiments we have found that this maximizes both efficacy and safety and we hope to see the same in humans."
The first organ to which colon cancer spreads is the liver and prognosis for patients with liver metastases of colorectal cancer is poor. So, the researchers chose tumors in the liver as the target for inserting the gene. "The procedure does not require surgery and is done with just local anesthesia to the skin," said Max W. Sung, MD, Medical Director for the Derald H. Ruttenberg Cancer Treatment Center and Assistant Professor in Hematology-Oncology at The Mount Sinai Medical Center. "Using one to three needles, the disarmed virus harboring the IL12 gene is injected through the skin into a metastatic tumor in the liver. We perform an ultrasound exam of the liver at the same time to track the needles in the liver so that we can deliver the virus to the correct location. The entire procedure can be completed within half an hour."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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