IU RESEARCHERS FIRST TO TEST GENE TRANSFER USING FIBRONECTIN PARTICLES IN TESTICULAR CANCER PATIENTS

INDIANAPOLIS -- Indiana University School of Medicine researchers are involved in a study that may hold hope for cancer patients whose treatment options are severely limited due to the advanced stage of their disease.

The first human trial using genetically engineered human protein fragments to enhance the transport of a retrovirus into normal bone marrow cells of patients with testicular cancer will be reported by researchers from the IU School of Medicine during the May 27-31 meeting of American Society of Gene Therapy in Seattle.

The human protein being used to bring together the retrovirus and the bone marrow cells is fibronectin, which was developed by researchers at the IU School of Medicine in collaboration with Takara Shuzo Co., Ltd, a biotechnology firm in Otsu, Shiga, Japan.

Nine patients have received the therapy to date in the Phase I trial. Within six months, it is hoped that a total of 15 patients will have undergone the therapy, said Rafat Abonour, M.D., principal investigator of the trial, assistant professor and medical director of the Indiana University Stem Cell Laboratory.

"The study is designed to see if this process enhances the transfer of the retrovirus containing therapeutic genes into bone marrow cells using the fibronectin," Dr. Abonour said. "It is too early to determine the efficacy of the trial, but the important thing at this point is that all nine patients have tolerated the procedure well."

The patients in the trial have refractory or relapsed germ cell tumor (testicular cancer) and have undergone bone marrow transplants and high dose chemotherapy. In the past, about half the testicular cancer patients whose disease returned have been cured by additional chemotherapy. Typically, bone marrow transplant patients who have relapsed are unable to receive the additional chemotherapy because repeated exposure to these toxic agents had destroyed their bone marrow cells. The result has been a dangerous delay in treatment or reduction of the dose of these drugs.

In this study, IU researchers are attempting to develop a way to make these patients tolerate additional, intense treatment. By introducing a gene called MDR-1 into the bone marrow cells, researchers hope to shield normal cells from further chemotherapy, thus enabling patients to receive the additional chemotherapy needed to eradicate residual disease and prevent return of cancer following bone marrow transplantation.

"MDR-1 works as a pump,"explained Dr. Abonour. "Every time the chemotherapy goes into the normal bone marrow cells, the MDR-1 will pump it out. That will prevent the death of the cells."

The fibronectin fragments are crucial to the process because they enhance the delivery of useful genes into bone marrow cells."

The fibronectin fragments are the glue that will allow the retrovirus to bind to the therapeutic cells," said Dr. Abonour. "They enhance the transfer of the retrovirus containing MDR-1 into bone marrow cells of cancer patients."

Bone marrow cells are essential for producing white blood cells to fight infection, red blood cells to carry oxygen and platelets to prevent bleeding. Maintaining an adequate number of these cells allows patients to receive chemotherapy without dangerous side effects such as infection or bleeding.

Contact: Mary Hardin
317-274-7722
mhardin@iupui.edu

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