Shanghai Cellular Therapy Group Announces Milestone Achievement with BZE2204: World’s First Triple-Target CAR-T for Hematologic Malignancies Achieves 100% Response Rate Without Chemotherapy-Based Lymphodepletion and Completed in Just 6 Hours

In the treatment of 8 patients with relapsed or refractory non-Hodgkin lymphomaBZE2204In the clinical trial (including 3 patients who received chemotherapy-free lymphodepletion CAR-T treatment), 7 patients achieved complete remission (CR), 1 patient achieved partial remission (PR), with an overall objective response rate (ORR) of 100% and a complete remission rate (CRR) as high as 87.5%.

Further data analysis revealed that, compared with currently marketed CAR-T products, the CAR-T cells in this drug group showed an over 100-fold increase in average proliferation capacity in vivo under the chemotherapy-based lymphodepletion regimen, with no observed cases of Grade ≥3 cytokine release syndrome (CRS) or neurotoxicity events. This positive outcome prompted further exploration into the clinical application potential of a chemotherapy-free lymphodepletion regimen. In the subsequent IIT (Investigator-Initiated Trial), three patients with refractory diffuse large B-cell lymphoma received JL-Flash CAR-T therapy using a chemotherapy-free lymphodepletion regimen. Results demonstrated an objective response rate (ORR) and complete response rate (CRR) both reaching 100%, with no occurrence of Grade ≥3 hematological toxicity, infection, CRS, or neurotoxicity.

It is reported that BZE2204 adopts a triple VHH domain design targeting CD19, CD22, and BCMA, simultaneously incorporating 4-1BB and CD3ζ intracellular signaling domains. The efficient gene transduction is achieved through the self-developed JL transposase system. Compared with traditional transposon technology, this technique offers significant advantages such as higher transposition efficiency, lower toxicity, and no insertion site preference.

In addition,BZE2204Based on “Flash CAR-T Platform"Development，Adopted an innovative ultra-short production process (only 6 hours,The traditional preparation cycle usually takes about 10 days.），Significantly simplified the operational process of personalized preparation, achieving a transformation from "complex" to "simple."This not only greatly reduces the preparation time and patient waiting period, but also effectively lowers the overall treatment cost.Secondly,This cellular drugWithout lymphodepletion chemotherapy, its proliferation capacity in the body still significantly outperforms the current commercially available CAR-T products under lymphodepletion conditions.Traditional CAR-T cell therapy usually requires pre-infusion chemotherapy conditioning to ensure the expansion and efficacy of CAR-T cells in vivo. However, many patients with relapsed or refractory tumors have severely compromised immune systems due to prolonged exposure to radiotherapy and chemotherapy, or autoimmune disease patients who have been on long-term immunosuppressants. If they undergo further chemotherapy conditioning, it will exacerbate pancytopenia and immune function damage.

Industry insiders pointed out,The currently marketed CAR-T drugs still face three core bottlenecks: lengthy preparation cycles, high production costs, and the risk of infection caused by lymphodepletion pretreatment. The global development of CAR-T therapy is undergoing a strategic transformation—shifting from the first phase, which prioritized curative treatment breakthroughs, to the second phase, focused on promoting accessible and widespread application. This shift aims to overcome the limitations of high costs and personalized customization, enabling CAR-T treatments to become truly accessible and beneficial to the broader population.

E.N.D

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