NEWS

Antibody solution may prevent adhesions after surgery

By LESLIE H. LANG
UNC-CH School of Medicine

CHAPEL HILL – Adhesions following gynecologic and abdominal surgery can be prevented by applying a special antibody solution at the end of the operation, according to new research conducted at the University of North Carolina at Chapel Hill.

The solution is aimed at neutralizing "sticky" molecules called alpha-v/beta-3 integrins, one member of a ubiquitous family of membrane glycoproteins involved in embryonic development, blood vessel formation, the immune system and wound healing.

"As gynecologists, we’re always concerned about post-surgical adhesions," said Dr. Bruce Lessey, associate professor of obstetrics and gynecology at the UNC-CH School of Medicine and a specialist in reproductive endocrinology and infertility. "Adhesion formation is a frequent complication of gynecologic and abdominal surgery and may result in infertility, ectopic pregnancy, chronic pain, prolonged recovery and intestinal obstruction."

Various methods have been tried to reduce post-operative adhesions, Lessey said.

"These include barriers, surgical technique, anti-inflammatory drugs, solutions and gels," he said. "This is currently a billion-dollar-a-year industry, and to date none of the proposed methods have been found sufficiently clinically effective for routine use during surgery as a way to reduce adhesions."

Lessey presented his findings Monday (Sept. 27) in a presentation to the American Society for Reproductive Medicine in Toronto, Canada.

"Few if any of the approaches to reduce post-operative adhesions has targeted cellular biochemistry to block the adhesion process," Lessey said.

On a rabbit experimental model, he and colleagues tested a solution containing the antibody LM609, developed by Dr. David Cheresh, professor at The Scripps Institute in La Jolla, Calif. This antibody targets the alpha-v/beta-3 integrin, which has been shown to be important in new blood vessel formation and tumor cell invasion. Cheresh, a pioneer in the field of integrins, discovered these integrins and produced the antibody, the humanized version known as Vitaxin, which is now undergoing clinical trials in people with advanced cancer.

"The antibody appears to be well-tolerated in human patients," Lessey said.

In the UNC-CH study, led by Lessey and members of the medical staff, Cheresh also collaborated. Among animals treated with the antibody solution were fewer, less extensive and less dense post-surgical adhesions compared to animals treated with a control antibody. Moreover, there was no statistical difference between adhesions in LM609-treated animals and animals that received a sham operation (surgically opened and then closed).

"We propose to use LM609 or its humanized counterpart, in collaboration with Dr. Cheresh, in a randomized, prospective trial of adhesion prevention in women undergoing laparoscopy for endometriosis and/or pelvic adhesive disease, Lessey said. "If this antibody can be shown to be efficacious in preventing adhesions in women, a larger multi-center approach will be organized.

"We hope it will be possible to prevent lesions before they form," Lessey added. "The implications of these neutralizing antibodies for surgery appear tremendous."

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School of Medicine contact :Lynn Wooten, (919) 966-6046/e-mail LWooten@unch.unc.edu.