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Tapping into regulatory T cells to improve outcomes for transplant patients

Although kidney transplantation is considered the best treatment for end-stage kidney disease, transplant patients still face high rates of mortality and morbidity in the long-term. These rates have remained largely unchanged over the last few decades.

“After a transplant, patients are on life-long immunosuppressive drugs that come with a lot of side effects, such as infection, cancer, and cardiovascular diseases,” says Dr. Caroline Lamarche, a nephrologist and researcher based at the University of Montreal, Canada.

“If we are going to improve the long-term outcome for patients, we need new strategies that support graft tolerance but avoid the need for non-specific immunosuppressive drugs.”

In her research, Dr. Lamarche aims to find the right balance between preventing graft rejection and minimizing the risks of immunosuppression. She believes this can be achieved with an alternative treatment called ‘Treg adoptive immunotherapy.’

Dr. Lamarche explains: “This means harvesting the patient’s own immune cells, modifying them in the lab, then putting them back into the patient’s bloodstream. This modification makes the cells more supportive of the transplanted kidney. Crucially, the patient’s immune system would still be functional elsewhere in the body, for example, to fight a lung infection or colon cancer.”

Instead of using drugs to broadly suppress the immune system, this technique makes the immune system more tolerant, but only towards the transplanted kidney.

In her talk at WCN’21, Dr. Lamarche will explain her work on these modified cells, called chimeric antigen receptor regulatory T cells or CAR Tregs. She will discuss their potential benefits for kidney transplant recipients and consider how and when this approach should be used.

“I am currently analyzing the impact that this modification has on the cells so that we can pick out those that are potent – and therefore useful for treatment – from others that are ‘exhausted.’ Understanding the difference will help us design the next generation of CAR Tregs for adoptive immunotherapy.”

Dr. Lamarche says that those who join her talk will learn more about the potential benefits and challenges that come with the use of donor-specific CARs Tregs in transplantation.

She adds: “By understanding the mechanisms behind this therapy, they will be able to critically analyze advances in this field. They will also be able to tell their patients that alternatives to the classic immunosuppressive drugs are under development and in clinical testing.”

Dr. Caroline Lamarche: “CAR-T reg therapy and the possibilities in transplantation” in the theme symposium: How can I prevent my transplanted patient from getting cancer and what should I do if they do? Sunday 18 April, 04.00-.5.00 hrs Montréal (Canada) time:!sessiondetails/0000014380_0

Monday 19 April, 14.00-15.00 hrs Montréal (Canada) time:!sessiondetails/0000013760_0

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