A human-made antibody successfully prevented organ rejection when tested in primates that had undergone a kidney transplant, report researchers.
The finding clears the way for the new monoclonal antibody to move forward in human clinical trials. Results of the study appear in the journal Science Translational Medicine.
“Current medications to prevent organ rejection are good overall, but they have a lot of side effects,” says lead author Imran J. Anwar, a surgical research fellow in Duke University’s department of surgery. “These therapies suppress the immune system, putting patients at risk of infections and organ damage, and many cause non-immune complications such as diabetes and high blood pressure.
“The push over the last 30 to 40 years has been to develop new, less toxic drugs,” Anwar says. “We are hopeful this antibody moves us closer to that goal.”
Anwar and colleagues, including co-senior author Allan Kirk, chair of the department of surgery, focused on a monoclonal antibody identified as AT-1501. It was engineered to minimize the risk of blood clots, which had become problematic for an earlier version of this therapy.
In studies using primates that had undergone kidney transplantation, AT-1501 prevented rejection without the need for additional immunosuppressive drugs or promoting blood clots, confirming its immunosuppressive potential.
In animals that had undergone islet transplantation, AT-1501 alone did not lead to uniform rejection control, but it was effective in combination with existing immunosuppressive agents. The combination therapies in islet transplantation led to uniform islet graft survival without weight loss or infections that can typically arise. Norma Kenyon, co-senior author and professor at the University of Miami, performed the islet transplantation.
“These data support AT-1501 as a safe and effective agent to promote both islet and kidney transplant survival and function and allow us to advance into clinical trials right away,” Kirk says. “This less toxic approach has been pursued for over 20 years, and I think we are finally at a turning point. This could be a great advance for people in need of organ transplants.”
The study received funding support from the National Institutes of Health, the Diabetes Research Institute Foundation, and Anelixis Therapeutics, now Eledon Pharmaceuticals, which is developing AT-1501 for kidney and islet cell transplant.
Source: Duke University