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Freiburg researchers have found a way to enhance the effect of a novel CAR T-cell therapy for leukemia and reduce the risk of cancer relapse / Publication in Nature Communications

Arming the body's own immune cells against cancer in the laboratory: this is the principle behind CAR-T cell therapy, which is already being used very successfully for certain treatment-resistant forms of cancer, such as acute lymphoblastic leukemia. However, the cancer recurs in some patients because the CAR-T cells are exhausted over time. Scientists from the Faculty of Medicine - University of Freiburg, together with Australian colleagues, have now shown in an animal model that the already approved drug azacitidine greatly reduces T-cell exhaustion and the risk of leukemia relapse. In addition, the CAR T cells recognize the cancer cells better when azacitidine is administered. The study was published on November 10, 2021 in the online journal Nature Communications.

"The combination treatment we have developed could be an important step towards helping many more cancer patients with CAR-T cell therapy," says Prof. Dr. Robert Zeiser, Head of the Department of Tumor Immunology and Immune Regulation in the Department of Medicine I (Medical Director: Prof. Dr. Justus Duyster) at the Medical Center - University of Freiburg and head of the German-Australian research team. In particular, the scientists were able to show that the recurrence of acute myeloid leukemia (AML) could be effectively prevented after CAR-T cell therapy. The drug used has an epigenetic effect, i.e. it removes genetic markers from the cells' genetic material and thus increases the activation of certain genes. As a result of the treatment, the cancer cells produced more of a certain surface protein, which in turn made them more easily recognized by the CAR-T cells. "The cancer cells' cloak is removed, so to speak, and they become visible to the immune system," says Zeiser. Further studies must now clarify whether the approach is also safe and effective in humans.

Original title of the study: Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia

DOI: 10.1038/s41467-021-26683-0

Link to the study:https://www.nature.com/articles/s41467-021-26683-0

Contact:
Prof. Dr. Robert Zeiser
Head
Department of Tumor Immunology and Immune Regulation
Department of Medicine I (Specialty: Hematology, Oncology and Stem Cell Transplantation)
Department of Medicine I (Specialties: Hematology, Oncology and Stem Cell Transplantation)
Phone: 0761 270-34580
robert.zeiser@uniklinik-freiburg.de