"Magic Bullets" find target in preliminary test of anti-rejection drug.

CHICAGO--(BUSINESS WIRE)--May 16, 1995--Kidney transplant patients studied at the University of California San Francisco showed almost no sign of rejection in a preliminary test of a new anti-rejection drug using humanized monoclonal antibodies -- sometimes called "magic bullets" for their ability to target and block the function of specific cells.

Flavio G. Vincenti, MD, UCSF clinical professor in the Kidney Transplant Service, reported the early results of a clinical trial of a product of molecular medicine against organ rejection today at the annual meeting of the American Society of Transplant Physicians.

The study evaluated a new drug known as HAT, or Humanized Anti-Tac. Tac refers to the specific region of immune system T-cells that the drug targets and blocks, preventing the cells from multiplying and attacking the transplanted kidney.

"Instead of attacking all of the cells and making the patient susceptible to infections, this drug only targets the cells that have recognized the foreign graft and have started to react to it," Vincenti explained.

HAT works by latching on to the interleukin 2 receptor that appears on the surface of the immune cells when they react to a foreign body, such as a transplanted kidney. By binding to the receptor, HAT blocks the interleukin protein essential to the proliferation of the immune cell from attaching to the site.

Although a Phase I clinical trial is designed primarily to test the safety, dose, and tolerability of a drug, the results of the study were also very encouraging in terms of the effectiveness of the drug, Vincenti said. A much larger Phase III trial is now under way to test the efficacy of the drug. The Phase III study, the first of two planned by the drug's sponsor, Hoffmann-La Roche Inc., will be conducted at transplant centers in the United States, Canada, Europe, and Australia.

UCSF is the only transplant center in Northern California using HAT in the current Phase III clinical trial.

In the preliminary study reported today, twelve patients received an intravenous dose of HAT before receiving a transplanted kidney and follow up doses four times after the procedure. Patients enrolled in the study also received conventional anti-rejection drugs.

Ten of the study patients received donated kidneys from relatives and two received cadaver organs.

Six months after their transplants, one of the patients who received a cadaver organ experienced a mild rejection episode and none of those who received organs from living-related donors experienced any rejection.

By comparison, six of the 16 kidney transplant recipients (38 percent) in a control group that did not receive HAT treatments suffered rejection episodes over the same period.

HAT was developed by Protein Design Labs Inc., of Mountain View, Calif., and licensed to Hoffmann-La Roche. Roche is also evaluating HAT in a Phase II/III study for the prevention of graft-versus-host disease, a condition common in certain patients who undergo allogeneic (non-self) bone marrow transplants. Graft-versus-host disease occurs when T-cells in the grafted marrow multiply and attack the patient's natural tissues.

One of the first fruits of biotechnology, monoclonal antibodies traditionally have been made by injecting mice with a target protein or infectious organism and then isolating and growing the cells that produce antibodies against the foreign substance. Though originally hailed as "magic bullets," antibodies derived from mice have been disappointing as drugs -- in part because humans make antibodies of their own that neutralize these mouse proteins. As a consequence, mouse antibodies typically can be given only once, which is rarely enough to prevent or treat disease.

Humanized monoclonals attempt to solve that problem. Using computer modeling and genetic engineering, Protein Design Labs combines the binding site of a mouse antibody, the small part of the antibody that attaches to its target, with 90 percent of a human antibody. The firm has developed similar antibodies for autoimmune and inflammatory disease, viral infections, certain cancers, and cardiovascular conditions.

UCSF has served as a major transplant center for Northern California for nearly 25 years and consistently ranks among the five most-active transplant centers in the country. Nancy Ascher, MD, PhD, is chief of the Kidney Transplant Service and the Liver Transplant Service. Other organ transplant programs at UCSF include kidney-pancreas, heart, and lung.

UCSF has been a leader in the testing of all major new anti-rejection drugs.

CONTACT: University of California, San Francisco 

Carol Fox or Bill Gordon, 415/476-2557