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Mount Sinai Investigators Developing a Novel Nanotechnology-Based Organ Acceptance Therapy

NOV 07, 2018 | EINAV KEET
A new study on a novel immunotherapy for organ transplant recipients has shown promising results, offering long-term organ acceptance without the dangerous side effects of the immunosuppressive drugs currently available.

The most commonly transplanted organs in the United States are the kidney, liver, heart, lungs, pancreas, and intestines. Transplant recipients receive organs from about 8,000 deceased organ donors each year, supplying about 28,000 organs, with an additional 6,000 organs from living donors. Although organ donation saves lives, organ transplant recipients must take ongoing immunosuppressive drugs to prevent organ rejection, part of the body’s natural immune response to a foreign object. When a transplant recipient receives a new organ, myeloid cells trigger the immune response, activating T-cells to attack the transplanted organ. The immunosuppressant medications that prevent this immune response also lower the body’s ability to fight infections and organ transplant recipients are at higher risk for certain types of cancer.

Now, a team led by investigators from the Mount Sinai School of Medicine say they’ve developed a revolutionary nanotechnology-based immunotherapy for organ transplant recipients that prevents organ rejection without the side effects of traditional immunosuppressant drugs. In a study, published on November 6, 2018, in the journal Immunity, the investigators found that their new nano-immunotherapy directly targets myeloid cells without affecting T-cells, preventing the activation of myeloid cells and triggering of T-cells that attack transplanted organs.

Testing their new nano-immunotherapy in mice receiving heart transplants, the investigators administered a short-term regimen of the new treatment without the use of standard anti-rejection drugs. They compared this group to mice with heart transplants that received the standard long-term anti-rejection treatment and those that received neither treatment and found that 100 days after the procedure, 75% of mice in the nano-immumotherapy-only group accepted the heart transplant. The mice receiving the standard therapy all had transplant rejection within 50 days, and all mice that received neither treatment rejected the transplant before day 10.

In an interview with Contagion®, co-lead investigator Jordi Ochando, PhD, explained the mechanism behind the experimental treatment.

“Our nanotherapy targets and deactivates myeloid cells in circulation. These cells are responsible for initiating organ transplant rejection. Interestingly, our nanotherapy also targets and deactivates the precursors of myeloid cells in the bone marrow. Therefore, once they leave the bone marrow they do not react against the transplanted organ,” Dr. Ochando said. “It’s like educating your kids before leaving home. It’s probably more efficient than trying to educate your kids after they move out and leave the nest.”

“Organ transplant patients take several pills day. Our experimental treatment is more potent at preventing organ rejection than 30 pills. Consequently, our treatment is less toxic. Reduced toxicity and side effects contributes directly in prolonging organ transplant survival and to increase the quality of life of transplant patients,” Dr. Ochando further explained on the long-term benefits of the treatment, noting that the research team stills need to investigate in detail the turnover of myeloid precursors in the bone marrow following their nanotherapy.

Co-lead investigator Willem J.M. Mulder, PhD, explained the team’s next steps toward advancing their treatment.

“We are planning to test our nano-immunotherapy in other transplantation mouse models and large animals as well,” Dr. Mulder said. “Nano-immunotherapies are a new class of immune system-regulating drugs that are highly specific, but relatively difficult to produce at large scale. With the support of the Mount Sinai leadership and Mount Sinai Innovation Partners, we are currently at the stage of establishing a biotech startup with the goal to initiate clinical trials within 5 years from now.”
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