ENHANCING RECOVERY IN ATHLETES WITH DLBCL: HUMANIZED CD19 CAR-T CELL THERAPY OVERCOMES RESISTANCE TO MURINE CAR-T BY MODULATING OXIDATIVE STRESS

Abstract

This study examines the therapeutic distinctions between humanized selective cluster of differentiation 19 chimeric antigen receptor (CD19hs CAR-T) cell therapy and murine CD19 CAR-T (mCD19 CAR-T) cell therapy in athletes with CD19-positive relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Notably, traditional mCD19 CAR-T therapy often fails to produce the desired remission in such challenging cases. This investigation involved four athletes who had not responded to mCD19 CAR-T therapy and were subsequently treated with CD19hs CAR-T therapy. Results indicated a significant reduction in oxidative stress levels in these patients, enhancing the CAR-T cells' tumoricidal activity and achieving complete remission. Furthermore, the study extended to a preclinical model where mice bearing human DLBCL HBL-1 cells were treated with various interventions including humanized CAR-T cells, murine CAR-T cells, blank T cells, and a solvent control. The assessment focused on the oxidative stress levels and the effectiveness of tumor cell eradication. The findings revealed that while murine CAR-T cells exhibited superior efficacy in reducing oxidative stress and attacking cancer cells compared to humanized CAR-T cells, the latter showed notable potential in clinical settings, especially for athletes whose physiological stress responses differ from the general population. Conclusively, the study supports the clinical application of CD19hs CAR-T cell therapy as a viable alternative for athletes suffering from CD19-positive relapsed/refractory DLBCL, particularly those unresponsive to conventional murine CAR-T therapies. This approach not only offers a potential for better management of lymphoma in athletes but also aligns with the sports medicine perspective by addressing the unique oxidative stress profiles in this population, thereby promoting a more tailored therapeutic strategy.