Petra Reinke: Reshaping undesired immune reactivity by regulatory T cells (Tregs)

As an internist in nephrology at the Charité University hospital in Berlin, I have been caring for organ transplant recipients for decades, mostly accompanying patients undergoing kidney transplantation. It has been inspiring to see how kidney transplantation has become a routine procedure with clear benefits for most patients, although each case is distinct and has its own varied challenges. Despite the improved one year data on transplant and patient survival, long term results are, unfortunately, still unsatisfactory. 

The main problems are that the lifelong necessary immunosuppression brings with it side effects (such as infections, cancer, metabolic and cardiovascular complications) and high direct and indirect costs (for example, for treatment of these side effects), while chronic rejection processes still cannot be sufficiently controlled. There is a great medical need for new, more effective, personalized immunosuppressive drugs combined with the earliest possible minimisation of immunosuppression.

This unmet medical need has motivated my research for a long time. However, aside from the rational reasons I have as a translation oriented clinician scientist to search for more personalised approaches in transplant medicine, as a treating physician, there is also an emotional motivation behind it. I have known many of my patients and their families for decades—some have had a functioning transplant for more than 30 years, whereas others have already received their third or fourth kidney. Over time, one becomes part of the family and knows their personal fates. 

How did I come to cell therapy?

We used the first cell therapy almost 20 years ago for treating/curing Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disease (PTLD) with virus specific T cells, which sparked my curiosity in this new treatment approach. The patient had previously had three EBV relapses, but after repeated T cell therapy doses they now had a well functioning transplant for almost 30 years. This was the trigger that inspired me to pursue research in cell and gene therapies. The introduction of new regulatory hurdles in the manufacture and use of advanced therapy medicinal products (ATMPs) has not made the road easy, but we have cleared the roadblocks and learnt a lot.

A burning question—how can we minimise immunosuppression as early and as much as possible ?  

In my opinion, this is a complex problem that can only be solved through close cooperation between many interdisciplinary teams of experts. In particular, the tool of EU funded research and Innovation Activity Projects is very well suited to approach such questions. In the ONE study consortium, different partners have developed and tested various new cell therapy approaches in order to reshape alloreactivity against transplants, which might then allow for the early minimisation of immunosuppression. This is a very important question that had to be answered.

The data from the first in human phase I/IIa study with our proprietary Treg product are presented here. It took three years to develop the good manufacturing practice (GMP) manufacturing method, but the investment has been worth it. We have succeeded in developing a new, robust manufacturing method that requires only 50 ml of blood as starting material. A one time application of Treg cells demonstrated immunoregulatory effects in the patient with no side effects. Importantly, the immunosuppression could be minimized in eight out of 11 patients after a few months, with a very good three year follow-up outcome.  

Future outlook

I would like to thank all of my patients and their relatives for trusting me, our entire team, and our scientific work. You have helped us to become much wiser. A starting point for a technology platform for next generation Treg approaches has been created, reaching from new (gene modified) Treg cell products to improved preclinical testing and new clinical applications. Next generation Treg approaches have now become the major focus of our new EU consortium Reshape (, opening up possibilities for further development of Treg therapy after organ transplantation, but also in autoimmunity and for the control of other undesired immune reactions, such as infections and immunogenicity of gene therapies.

Petra Reinke is an internist and professor in nephrology and transplant medicine at the Charité University Hospital in Berlin. Petra is the founding director of the Berlin Center for Advanced Therapies (BeCAT; and head of the immunology platform and part of the steering committee of the Berlin Institute of Health Center for Regenerative Therapies (BCRT;

Competing interests: See linked paper.