Novel Promoter Strategy Enhances Safety and Efficacy of CAR-T Therapy in Acute B Cell Leukemia

Beijing, China – July 23, 2024 – In a groundbreaking development, Lu Daopei Hospital, in collaboration with Hebei Senlang Biotechnology, has unveiled promising results from their latest study on chimeric antigen receptor T (CAR-T) cell therapy. This study, which focuses on the efficacy and safety of CAR-T cells engineered with different promoters, marks a significant advancement in the treatment of relapsed or refractory acute B cell leukemia (B-ALL).

The study, titled "Promoter Usage Regulating the Surface Density of CAR Molecules May Modulate the Kinetics of CAR-T Cells In Vivo," explores how the choice of promoter can influence the performance of CAR-T cells. Researchers Jin-Yuan Ho, Lin Wang, Ying Liu, Min Ba, Junfang Yang, Xian Zhang, Dandan Chen, Peihua Lu, and Jianqiang Li from Hebei Senlang Biotechnology and Lu Daopei Hospital spearheaded this research.

Their findings indicate that using the MND (myeloproliferative sarcoma virus MPSV enhancer, negative control region NCR deletion, d1587rev primer binding site replacement) promoter in CAR-T cells leads to lower surface density of CAR molecules, which in turn reduces cytokine production. This is significant because it helps to mitigate the severe side effects often associated with CAR-T therapy, such as cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES).

The clinical trial, registered under ClinicalTrials.gov identifier NCT03840317, included 14 patients divided into two cohorts: one receiving MND-driven CAR-T cells and the other receiving EF1A promoter-driven CAR-T cells. Remarkably, all patients treated with MND-driven CAR-T cells achieved complete remission, with most of them showing minimal residual disease-negative status after the first month. The study also reported a lower incidence of severe CRS and CRES in patients treated with the MND-driven CAR-T cells compared to those treated with EF1A-driven cells.

Dr. Peihua Lu from Lu Daopei Hospital expressed optimism about the potential of this novel approach, stating, "Our collaboration with Hebei Senlang Biotechnology has yielded crucial insights into optimizing CAR-T cell therapy. By adjusting the promoter, we can enhance the safety profile of the treatment while maintaining its efficacy. This is a significant step forward in making CAR-T therapy more accessible and tolerable for patients."

The study was supported by grants from the Natural Science Foundation of Hebei Province and the Department of Science and Technology of Hebei Province. It highlights the importance of promoter selection in the development of CAR-T cell therapies and opens new avenues for safer and more effective cancer treatments.