Why some tumors are resistant to cell therapies

LOEWE, the federal state of Hesse’s research promotion program for the development of scientific and economic excellence, is providing 4.8 million in funding for a new research network spearheaded by Goethe University. The LOEWE research cluster CARISMa focuses on new therapies that use genetically modified endogenous immune cells, so-called CAR-T cells, to treat therapy-resistant types of cancer.

In congratulating the CARISMa scientists, Goethe University President Prof. Enrico Schleiff said: “The new LOEWE network sets up in Hesse an innovative research program that is currently gathering steam all over the world. It also expands Goethe University’s existing research profile and broadens our network of cooperation partners in the field of CAR cell therapy [editor’s note: CAR is the abbreviation for chimeric antigen receptor]. The network deliberately builds on our university’s existing strengths in tumor biology, drug development and clinical oncology. In addition, our ‘Molecular and Translational Medicine’ profile area will also receive new impetus from the cell therapy focus.”

The field of cell therapy is one of the most dynamic areas of modern hematology and oncology. During CAR therapy, the patient’s own immune cells are genetically modified through the introduction of the CAR vector, enabling them to specifically recognize and immunologically kill tumor cells. CAR therapy has been successful in the treatment of leukemia and lymphoma where previous therapies have failed. So-called “solid” tumors, including malignant brain, pancreatic and intestinal tumors, on the other hand, have proven to be largely resistant to this therapy.

The new LOEWE focus “Optimization of CAR cell therapies by influencing the immunosuppressive tumor microenvironment”, or CARISMa for short, seeks to contribute to a better understanding of how this resistance of solid tumors comes about and how it can be prevented. The research focuses on how exactly CAR-T cells interact with the tumor and its tumor microenvironment and how novel CAR cell therapies can be developed to overcome this resistance. To this end, the project partners, who are already conducting joint research, will work even more closely together, transcending sites and disciplines.

In addition to Goethe University Frankfurt, the other partners in CARISMa are Philipps-Universität Marburg, the Georg Speyer Haus Institute for Tumor Biology and Experimental Therapy, the Paul-Ehrlich-Institut (the Federal Institute for Vaccines and Biomedicines), as well as the blood donor service of Baden-Württemberg-Hessen. The new LOEWE focus will also create synergies based on its cooperation with the German Cancer Consortium (DKTK) and Frankfurt Cancer Institute (FCI), also a LOEWE center.

CARISMa’s scientific coordinator is Prof. Thomas Oellerich from Goethe University Frankfurt’s Faculty of Medicine, Medical Clinic II, and Frankfurt University Hospital. The research project will receive around €4.8 million in funding for four years, from 2025 to 2028.

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