CD24 targeting with NK‐CAR immunotherapy in testis, prostate, renal and (luminal‐type) bladder cancer and identification of direct CD24 interaction partners

• DOI: 10.1111/febs.16880
• Publication Date: 2023-05-31T07:19:00Z
• Authors: Christian Söhngen; David J. Thomas; Margaretha A. Sko...; Felix Bremmer; Markus Eckstein; Anja Stefanski; Marc D. Driessen; Gamal A. Wakileh; Kai Stühler; Peter Altevogt; Dan Theodorescu; Rüdiger Klapdor; Axel Schambach; Daniel Nettersheim
• Keywords: CD24; Viability assay

Alternative therapeutic options targeting urologic malignancies, such as germ cell tumours, well urothelial, renal and prostate carcinomas, are still urgently needed. The membrane protein CD24 represents a promising immunotherapeutical approach. present study aimed to decipher the molecular function of in vitro evaluate cytotoxic capacity third‐generation natural killer (NK) chimeric antigen receptor (CAR) against tumour lines. Up 20 lines several non‐malignant control cells were included. XTT viability assays annexin V/propidium iodide flow cytometry analyses performed measure apoptosis rates, respectively. Co‐immunoprecipitation followed by mass spectrometry identified direct interaction partners CD24. Luciferase reporter used functionally validate transactivation expression SOX2. N ‐ O ‐glycosylation evaluated enzymatic digestion spectrometry. demonstrates that SOX2 transactivates embryonal carcinoma cells. In different urological origins, interacted with proteins involved adhesion, ATP binding, phosphoprotein binding post‐translational modifications, histone acetylation ubiquitination. Treatment NK‐CD24‐CAR resulted decreased induction specifically + Limitations include setting, which has be confirmed vivo . conclusion, we show is novel target for immune approaches malignancies.