生产过程中一致的体外细胞增殖可预测 CAR-T 细胞治疗后的良好结局

Efficacy of chimeric antigen receptor (CAR) T-cell therapy hinges on CAR-T potency, as well as on tumour traits and disease status. Potency assessment currently relies on post-infusion in vivo growth; therefore, manufacturing metrics could provide early potency predictions, enabling potency-guided strategies. To assess the impact of ex vivo cell growth during manufacturing on clinical outcomes, we analysed diffuse large B-cell lymphoma patients treated with tisagenlecleucel, merging clinical records with manufacturing parameters. Of 75 cases, 21 (28%) showed poor growth, indicated by any decrease in cell number during manufacturing. Good growth correlated with significantly better overall response rate (85.

2% vs. 52. 4%; p = 0. 006), with enhanced lymphocyte increase in peripheral blood after infusion. Multivariate analysis revealed that this group had significantly higher progression-free survival (PFS) (adjusted hazard ratio [aHR]: 0. 377; 95% confidence interval [CI]: 0. 180-0. 789; p = 0. 010) and overall survival (OS) (aHR: 0.

191; 95% CI: 0. 071-0. 510; p = 0. 001), with lower cumulative incidence of disease progression (aHR: 0. 412; 95% CI: 0. 198-0. 858; p = 0. 018), compared to the poor growth group, even after adjusting for clinical factors, bridging therapies performed between apheresis and infusion and disease status at infusion.

Our findings suggest that good cell growth during manufacturing predicts favourable post-CAR-T outcomes. Identifying clinical factors that influence manufacturing parameters could improve post-CAR-T outcomes.