Mayo Clinic is advancing cell-based transplant research aimed at reducing patients’ long-term dependence on anti-rejection drugs, with several approaches now moving towards broader efficacy testing.
The work targets a longstanding limitation of organ transplantation. Recipients typically require immunosuppressive medicines from the time of surgery because the immune system recognises a donated organ as foreign and begins attacking it. These drugs have transformed transplant outcomes, but their broad effect on the immune system can also increase the incidence of infections, certain cancers, diabetes and hypertension.
The next stage of transplant medicine is therefore focused on achieving a more selective immune response. Rather than suppressing immune activity across the body, researchers are seeking to retrain the immune system so that it tolerates a specific donated organ while retaining its ability to respond to infections and cancer.
Mayo Clinic is pursuing this objective through several cell-based approaches. One programme has involved regulatory T cells, a type of white blood cell that helps control other immune cells. The aim is to use these cells to reduce the immune attack on a transplanted organ and create conditions in which immunosuppressive treatment can eventually be lowered.
The liver is currently the most practical testing ground for this strategy because it has a greater natural capacity for immune tolerance than other transplanted organs. Liver recipients can often reduce their medication burden after transplantation, and some patients have been able to stop immunosuppression under carefully controlled conditions. That biological advantage gives researchers an opportunity to test whether tolerance can be deliberately induced rather than occurring naturally in a limited number of patients.
Another approach being explored involves chimerism, in which donor immune cells are introduced into a transplant recipient so that donor and recipient immune systems can coexist. The objective is to familiarise the recipient’s immune system with the donor before or around transplantation, reducing the likelihood that the donated organ will subsequently be attacked.
The broader field has already produced early clinical evidence supporting continued development. Research at the University of Pittsburgh has involved regulatory immune cells collected from living liver donors and infused into recipients before or after transplantation. Some patients in those studies were able to stop immunosuppressive drugs completely and remained off the medicines for three or more years.
Verici Dx Plc (LON:VRCI) is developing a complementary suite of proprietary, leading-edge tests forming a kidney transplant diagnostics platform for personalised patient and organ response risk to assist clinicians in medical management for improved patient outcomes.
