Recently, Lu Daopei hospital and Gracell Bio jointly published a research article entitled “next day manufacturing of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first in human clinical study” in the authoritative academic journal in the field of blood cancer (latest if=9.81), The results of a clinical study of fastCAR-T cell therapy for CD19 positive recurrent / refractory acute B-lymphoblastic leukemia were presented.
At present, the main problems in the preparation of traditional CD19 CAR-T are: long cycle, requiring 7-14 days of production time; High cost; T cell failure and other problems. In order to improve clinical results and shorten the preparation time of CAR-T cells, Genxi biological developed fastCAR-Tplatform.
FastCAR-Tunder the new mode can realize “production is completed the next day”, which greatly shortens the preparation time; In addition, fastCAR-Tcells have the following characteristics: stronger amplification ability, younger cell phenotype, less cell failure, and stronger tumor killing effect.
In preclinical studies, compared with traditional CAR-Tcells, CD19 fastCAR-T cells showed excellent growth ability, younger cell phenotype, less depletion and more effective tumor clearance.
In the phase I clinical study (nct03825718) conducted in Lu Daopei hospital, 25 patients with refractory / recurrent B-ALL were enrolled, including 5 children under the age of 14. FastCAR-Tcells were 100% prepared successfully, 25 patients all got infusion.
The results of phase I clinical study showed that the safety of CD19 fastCAR-T was controllable. 24 patients (96%) developed CRS, including 18 patients (72%) with grade 1-2 CRS and 6 patients (24%) with grade 3 crs. There was no grade 4 or higher CRS. In the >14-year-old group, 16/20 (80%) patients had mild CRS, and only 2/20 (10%) patients had grade 3 crs. For patients ≤ 14 years of age, 2/5 (40%) had mild CRS, but 3/5 (60%) had grade 3 crs. Icans was observed in 7 (28%) patients, of which 2 (8%) grade 3 icans occurred in patients over 14 years old, and 5 (20%) grade 4 icans occurred in patients under 14 years old. 14 days after fastCAR-T infusion, 23/25 (92%) patients achieved complete remission (CR) with minimal residual disease (MRD) negative, and then 20 patients were done with allogeneic hematopoietic stem cell transplantation (allo HSCT) within 3 months after fastCAR-T treatment. Among the 20 patients, 15 (75%) were still in disease-free survival, and the median duration of remission was 734 days. One patient relapsed and 4/20 died of transplant related death. Among the 3 patients who did not receive allo HSCT, 2 patients were still in CR status at the 10th month of follow-up after fastCAR-T treatment.