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A clean room for gene therapy and stem cell transplantation

Yale Medicine Magazine, 1999 - Winter


In 1989 leukemia patient Richard D. Frisbee III became the first child in Connecticut to receive a bone marrow transplant. He died later that year, but were he alive today he might be a candidate for a stem cell transplant, which has emerged as a promising way to halt leukemia and other cancers. To help pursue new treatments and honor this young patient, the Richard D. Frisbee III Laboratory of Stem Cell Transplantation and Hematopoietic Graft Engineering opened in October at Yale-New Haven Hospital’s Blood Bank in the Department of Laboratory Medicine.

A “clean room” laboratory for gene therapy and stem cell manipulations, the Frisbee Laboratory will be used for both clinical applications and basic science research by a number of medical school departments and the Yale Cancer Center. “It is literally a biological manufacturing facility,” says Edward L. Snyder, M.D., the blood bank’s director and a professor of laboratory medicine. “This unique laboratory provides an opportunity to link together the Yale Cancer Center, Yale-New Haven Hospital and the School of Medicine in a three-pronged attack against cancer.”

In the new Class 10,000 laboratory—so named because it has fewer than 10,000 dust particles per cubic foot of air—Yale physicians and scientists will have a cleaner environment in which to process stem cells from the blood or bone marrow of both patients and donors. After chemotherapy, a patient’s previously collected stem cells are reinfused and migrate to the bone marrow, where they reproduce and differentiate, creating blood cells that commit to specific functions in the body. For stem cell transplants for patients who do not have a “matched” donor, T cells can be removed from donor blood or bone marrow to prevent graft-versus-host disease in recipients. “We need to be in a special environment with purified air so that we do no harm to the cells when we are doing our manipulation,” says Diane Krause, M.D., Ph.D., assistant professor of laboratory medicine and director of stem cell processing at the Blood Bank at Yale-New Haven Hospital.

Stem cell therapy is especially promising because “rather than trying to beat the disease to death with chemotherapy, it allows us to step back and apply a more gentle treatment,” says Dennis Cooper, M.D., HS ’82, clinical director of stem cell transplantation at the Yale Cancer Center. He says that work by investigators including Joseph P. McGuirk, D.O., and Stuart E. Seropian, M.D., is pushing the limits of existing therapies. By manipulating stem cells to attack tumor cells through an immunologic response, these new therapies give patients a much better chance of surviving after being diagnosed with cancer. “The most exciting area in the next 10 years,” Dr. Cooper says, “is going to be in identifying the different cell types that can attack the tumor without harming the patient. The Frisbee lab is where many of these cell manipulation studies will be done.”

As the field of gene therapy matures over the next five to 10 years, the laboratory will provide a facility for testing newly designed vectors, the altered viruses that are used to deliver therapeutic genes in the treatment of cancers and other diseases. (Yale has another Class 10,000 clean room in the Sterling Hall of Medicine that is also used for basic research in gene therapy, under the directorship of Albert Deisseroth, M.D., Ph.D.)

Creation of the Frisbee Laboratory was made possible through the fund-raising efforts of Christine Frisbee, Richard’s mother and former administrator of the stem cell transplant unit at Yale. In 1990, she launched a foundation named for her son, which, since then, has raised and distributed more than $1 million. The new laboratory is the foundation’s largest undertaking to date. “We want to fund things that other people won’t fund, that we think are innovative and that bring the field of transplantation forward,” she says.

The foundation also provided support for the First Annual Frisbee Foundation Stem Cell Symposium, held in October to coincide with the opening of the Frisbee Laboratory. Speakers discussed cord blood processing and its effect on stem cell transplantations, advances in breast cancer research and graft-versus-host disease. “Our aim,” says Ms. Frisbee, “is to get people who are doing the most advanced research to educate other health care professionals with the hope that more people will use this knowledge to help find cures.”

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