CELL INTELLIGENCE · 肿瘤细胞治疗研究

In 2014, the first patient received a CD22 chimeric antigen receptor (CAR) T-cell product. As one of the earliest approaches targeting an antigen other than CD19, this trial addressed an unmet need while providing insights into CAR T-cell efficacy, impact of manufacturing changes, and management of inflammatory toxicities over its 10-year span. This final chapter provides a comprehensive review of the collective findings. Across 78 patients with B-cell acute lymphoblastic leukemia who received infusion, cytokine release syndrome was observed in 66 (84. 6%) patients, whereas 28 (35.

9%) had immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), and 18 (23. 1%) had reversible neurotoxicity. Complete response was achieved in 54 (70. 1%) patients by day 28, of whom 45 (83. 3%) were measurable residual disease negative. Median overall survival was 13.

6 months, and median relapse-free survival was 6. 1 months. Pharmacokinetics revealed peak CAR T-cell expansion at a median of 14 days (range, 12-50), with no variation by dose. Interestingly, toxicities, CAR T-cell expansion, and disease response did not correlate with baseline disease burden.

Additionally, although early intervention approaches to mitigate IEC-HS severity for this construct appeared promising, further study is needed. Given the critical importance of CD22 targeting, this experience serves as a foundation for new approaches targeting CD22 while providing ongoing support for dual-targeting approaches and insights into toxicity mitigation. This trial was registered at www. ClinicalTrials. gov as NCT02315612.