次日制备的新型 CD19 CAR-T 细胞用于急性淋巴细胞白血病

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL).

However, challenges remain including long manufacturing processes that need to be overcome.

We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19 + R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy.

We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100. 00%) by day 28, with 17 of the patients (94. 4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83. 3%) remained disease free at the 3-month assessment, 14 patients (77. 8%) maintaining MRD negative at month 3.

Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899. 5/ g DNA and a median persistence period of 56 days (range: 7-327 days). The incidence of cytokine release syndrome (CRS) was 95. 2% (n = 20), with severe CRS occurring in 52. 4% (n = 11) of the patients. Six patients (28. 6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells.

Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.