Personalising immunosuppressive therapy

Organ transplantation is often the only cure for end-stage organ failure. Advances in pharmacologic immunosuppressive treatments support short-term graft survival, but long-term graft and patient survival rates are unsatisfactory.

Clinical practice has moved from increasing immunosuppression to minimising the use of immunosuppressive drugs as early as possible. However, the decision is based on observational studies with hardly any molecular or immunological information.

In answer to this, the EU-funded BIO-DRIM project aims to develop biomarker-driven strategies for personalising immunosuppression. The consortium proposes that by characterising individual immune response profiles and by monitoring tolerance induction, one would minimise the risk of over-suppression. This approach would prospectively stratify transplant patients based on their individual immunosuppression needs, hopefully minimising graft toxicity, acquired infections, and other co-morbidities such as diabetes and cardiovascular events.

The biomarker-driven management of immunosuppressive therapy builds on advances made in the predecessor projects IOT and RISET, which had selected a number of promising biomarkers. The BIO-DRIM project aims to continue this work and implement the use of biomarkers in the clinic.

To meet their objectives, BIO-DRIM research teams will carry out 5 clinical trials on over 1 000 enrolled patients who have received liver or kidney transplants and different doses of immunosuppression. Using a set of different and professional validated biomarkers, they plan to evaluate the impact of immunosuppressive therapy withdrawal.

Researchers are performing experiments in a mouse model of acute rejection to shed light into the mechanisms underlying the benefits associated with reduced immunosuppression. This part of the project has already implicated T cells and should lead to the identification of new biomarkers associated with chronic rejection or tolerance.

The use of biomarkers to personalise immunosuppressive therapy is a novel approach. Initial data from BIO-DRIM work suggest that at least 10 % of long-term transplant patients could benefit from this approach, minimising health care costs and improving transplant outcome.