Scientific success in cancer therapy in Debrecen 05. Mar. 2024

The January issue of Nature Reviews Clinical Oncology published a summary paper summarising perspectives on the use of chimeric antigen receptor gene-edited immune cell therapies for organ tumours (so-called solid tumours). The paper’s author is Steven M. Albelda, Principal Investigator, Center for Immune Cell Therapy, University of Pennsylvania. The article refers to a finding published in August 2021 by researchers at the Institute of Biophysics and Cell Biology at the University of Debrecen's Faculty of General Medicine, which provides recommendations for clinicians on the composition of cell therapy.

- The summary paper in the high impact journal cites our results in two places, highlighting their importance. This indicator shows the prestige of a scientific journal, i.e. the impact factor on science, which shows the average number of times an article published in a journal has been cited in a given period. The impact factor for Nature Reviews Clinical Oncology is very high, indicating that papers published in the journal have a significant influence on medicine as a whole, and on oncology in particular. The journal is a key source of information for clinical oncologists, researchers and decision-makers alike," Árpád Szöőr, Adjunct Professor at the Institute of Biophysics and Cell Biology, Faculty of General Medicine, University of Debrecen, told

The author of the article, Professor Steven M. Albelda, is a major figure in the field and a leading researcher at the University of Pennsylvania, which has played a key role in research into therapies based on genetically modified immune cells, known as CAR T-cells. Professor Carl H. June , is the founder of the Center for Immunotherapy at the American university whose work was recognized by the Faculty of General Medicine in 2015 with the Debrecen Prize for Molecular Medicine.
- CAR T-cell therapies have shown significant success primarily in the treatment of haematological, blood-related cancers such as leukaemias and lymphomas. However, the use of this therapy in organ tumours is facing challenges at several points. Professor Albelda summarised in his communication the major scientific advances of the last few years that either help to understand the ineffectiveness of CAR T cells in organ tumours or provide lessons that should be taken into account when designing and manufacturing effective therapeutics. Our results fall into this second category," said the asssitant professor at the University of Debrecen.

The publication of the University of Debrecen researchers in 2021, first authored by PhD student Marianna Csaplár with corresponding authors Professor György Vereb and Assistant Professor Árpád Szöőr, is the result of a collaboration with an international industrial partner, Takara Bio Inc. As a result of a systematically designed series of experiments on tumour cell cultures and animal models, a clear recommendation was made for clinicians on the composition of T cell preparations for organ (solid) tumours to achieve a more successful therapeutic outcome.

- The value of our work is further enhanced by the fact that it dared to go against the then prevailing view which considered the cell-type composition of therapeutic agents successfully used in leukaemias to be generally valid and adaptable to organ tumours without modification. We were the first to publish that these organ tumours require a completely different approach and that, instead of the less aggressive but long-lasting cell formulations that have been shown to be preferable in leukaemias, aggressive cells with significant killing potential should be used early in the antitumour response to achieve a greater therapeutic effect, even at the cost of possibly depleting these cells sooner. This finding was confirmed by another research team shortly after us and more recently by Professor Albelda's colleagues. For this reason, the result has been given considerable weight in the summary statement," said Professor György Vereb, head of the research team.

The working group at the University of Debrecen is currently focusing on solving the problems identified in the field of CAR T cell therapies targeting organ tumours. In a Hungarian industrial collaboration, they are investigating new types of therapeutic targets and the molecules that can effectively attack them. They are also investigating what can be done in cases where therapy becomes ineffective because the tumour no longer presents the target that the CAR T cell recognises. Universal CAR T cells, developed by the Debrecen team, could provide a solution.

An important barrier to the dissemination of CAR T cell therapies is their almost exclusive customized application. This means that each cancer patient must receive a cell preparation specifically made from their own blood. This makes manufacturing difficult, slow and expensive. Researchers in Debrecen are also working on developing a therapy based on natural immune killer cells that could overcome this problem.

Link to the international publication (the University of Debrecen researchers' publication is shown as reference 98).
Link to the first-authored communication by Marianna Csaplár, with corresponding authors György Vereb and Árpád Szöőr.

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