Research Corporation Technologies
101 N. Wilmot Road, Suite 600
Tucson, Arizona 85711-3365
(520) 748-4400, (520) 748-0025 fax
http://www.rctech.com
From:
Jan McCoy Hutchinson, (520) 748-4458 E-mail: [email protected]
Contact:
Shaun A. Kirkpatrick, RCT Venture Development Associate, Tel. (520) 748-4446, Fax (520) 748-0025, [email protected]
Antirejection Antibody Could End Lifelong Use of Immunosuppressants --RCT Seeks Partner or Licensee to Help Move the Antibody Into Clinical Trials
(TUCSON, Ariz.) Ongoing preclinical studies of an antirejection antibody have established its ability to prevent and reverse organ rejection while leaving the immune system intact. The CD45RB antibody induces antigen-specific tolerance that may allow transplant patients to stop the chronic use of toxic immunosuppressive drugs. The antibody also shows promise for use with autoimmune diseases.
Rejection continues to be the major impediment to successful organ transplantation. Current transplant technology requires chronic use of steroids and global immunosuppressants, such as cyclosporine, to prevent rejection. These drugs leave patients vulnerable to infection, cancer and other diseases. Antibodies to reverse or delay rejection, such as Orthoclone OKT3Æ, eliminate most of the body's lymphocytes and so are given only acutely. Besides the serious side effects, present immunosuppressant therapy is only partially successful. About 60 percent of kidney transplant patients have at least one rejection episode in the first three months after surgery. None of the current immunosuppressive agents offer the hope of immune tolerance without chronic immunosuppressant use.
The antigen-specific tolerance created by the CD45RB antibody presents a safe, new approach to preventing and treating transplant rejection and autoimmune diseases in humans.
Although the mechanism is not completely understood, the antibody interrupts the immune activation process without depleting the entire T cell population. It reacts to a specific epitope on the CD45RB isotype, a subpopulation of cells that activate in response to particular antigens. This antibody was developed by Andrew I. Lazarovits at the University of Western Ontario and Sibrand Poppema of the University of Groningen in the Netherlands. Lazarovits recently received the prestigious Medal for Research Excellence from The Kidney Foundation of Canada for his internationally recognized work.
Through its Venture Development Group, Research Corporation Technologies has collaborated with Lazarovits and Poppema to follow up on their earlier work and conduct the preclinical studies needed to advance the technology. RCT's preclinical development plan builds on results the researchers published in the April 1996 issue of Nature. In those studies, mice given a short course of therapy with the CD45RB antibody at surgery survived kidney transplants and had normal renal function without additional treatment. A second group of mice that received transplants with no immunosuppressive therapy developed acute rejection that the CD45RB antibody reversed.
Results from the preclinical studies show that a short course of the CD45RB antibody induces tolerance in mice to hearts and pancreatic islets transplanted from the same (allografts) and different (xenografts) species. The antibody also prevents diabetes in mice predisposed to the disease and prevents autoimmune encephalitis, a model of multiple sclerosis. Preliminary results from studies of other disease models, such as arthritis, are encouraging. Initial data from ongoing kidney transplant studies using a mouse anti-human CD45RB antibody in monkeys also look favorable. The results are similar to Lazarovits and Poppema's rodent kidney studies published in Nature showing transplant rejection reversal and indefinite animal survival.
Other key researchers working on the preclinical studies with RCT include Robert Z. Zhong at the University of Western Ontario, David M. Rothstein and Giacomo P. Basadonna at Yale University, and Joel Schiffenbauer at the University of Florida.
RCT now seeks a partner or licensee to help move the CD45RB antibody into clinical trials. To do this, the mouse antibody may need to be chimerized, humanized or a human CD45RB antibody developed. Humans normally develop an immune response against the murine portion of a mouse-derived antibody that can render the therapy ineffective.
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RCT is an independent technology management company that commercializes technologies from universities and research institutions throughout North America.
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