Interview with Martin Szyska

In December, BIH Johanna Quandt Professor Il-Kang Na and Martin Szyska were awarded with the Paper of the Month.

What are you researching? What is the core of your research?

Our research focuses on methods to improve the adoptive T-cell therapy (ATT) for an even more efficient treatment of cancer. To this end, we have developed a method that can be used to analyze in detail the efficacy and limitations of previous T cell therapy forms. The information obtained from that allows us to draw valuable conclusions as to which combination of therapies used concurrently with ATT shows the best effects against tumors. Our mission is to improve on an ingenious idea, which T cell therapy undoubtedly is, to the point that it will help cure as many patients as possible.

What is the core message of your publication and how does your study differ from the work of other scientists in this field?

Whereas previous approaches to monitoring the T cell response allowed only for migration and proliferation of the injected immune cells, our new method provides the ability to capture in the body both the migration and the activation of T cells over a long period of time. This is of utmost importance because in many cases the function of T cells is switched off only after they have migrated to the tumor, which is how cancer protects itself against therapy. Our bioluminescent reporter model offers the opportunity to investigate which therapy approaches can effectively suppress this type of tumor defense.

Which cooperation partners have contributed to the publication? Who was significantly involved?

Our method is based on a transgenic reporter construct developed by Dr. Il-Kang Na in Marcel van den Brink Laboratory at the Memorial Sloan Kettering Cancer Center in New York City. The current work was developed in close collaboration with Prof. Blankenstein’s working group at Max Delbrück Center of Molecular Medicine (MDC) as part of SFB-TR36.

What are the next steps planned for the project and what are the possible implications of your results for patients?

In this publication, we demonstrated the applicability of our NFAT reporter in a clinically relevant tumor model. Our main goal now is to use the advanced capabilities of our method to investigate which combination of T cells used with other modern cancer therapies, such as checkpoint inhibition, promises optimal anti-tumor efficacy and hence the best possibility of a cure. For this purpose, it is imperative to use our methods to gain better insight into defense strategies during the development of the disease, in order to be able to attack with the right therapy at the right time.

In addition to optimizing combination therapies, our model can also help better understand under what circumstances ATT is directed against the patient’s healthy tissue, and how to best suppress this toxic side effect. Furthermore, our method provides new insight into the maturation processes of T cells in the thymus, which is being investigated in a follow-up project.