尽管嵌合抗原受体T细胞疗法（CAR-T）用于T细胞恶性肿瘤的临床试验处于早期阶段，但显示出为难治性/复发性（R/R）T细胞恶性肿瘤患者提供长期缓解的重要潜力。在我们的Ⅰ/Ⅱ期临床试验中，共招募了65名R/R T细胞急性淋巴细胞白血病和淋巴母细胞淋巴瘤（T-ALL/LBL）的儿童和成人患者（NCT04572308和NCT04916860）。其中60名参与者（T-ALL 35例，T-LBL 25例）在三个水平上接受了一剂天然选择的抗CD7 CAR（NS7CAR）T细胞，剂量分别为低剂量（5×105/kg）、中剂量（1到1.5×10^6/kg）和高剂量（2×10^6/kg）。第28天，94.4%的患者在骨髓中达到深度完全缓解（CR）。在32名有异质性病变的患者中，78.1%显示出反应，其中56.3%完全缓解，21.9%部分缓解。2年总生存率和无进展生存率（PFS）分别为63.5%（95% CI 47.7-79.4）和53.7%（95% CI 38.9-68.6），儿童和成人患者之间无差异。在37名完成巩固移植的CR患者中，PFS明显高于10名未完成移植的患者，1年PFS分别为67.2%（95% CI 51.9-82.4）和15.0%（95% CI 0-40.2），p < .0001。未移植的10名CR患者中，8名复发，而2名分别在第128天和第180天保持CR。细胞因子释放综合征发生率为91.7%（80.0%为1/2级，11.7%为3/4级），5%的患者出现神经毒性。NS7CAR-T疗法在治疗R/R T-ALL/LBL患者中具有显著的疗效和有希望的PFS，同时具有可控的安全性。© 2023 Wiley Periodicals LLC.

While the use of chimeric antigen receptor-T (CAR-T) therapy for T-cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long-term remission for patients with refractory/relapsed (R/R) T-cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T-ALL 35, T-LBL 25) received a single dose of naturally selected anti-CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 105 /kg), a medium dose (1 to 1.5 × 106 /kg), and a high dose (2 × 106 /kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2-year overall survival and progression-free survival (PFS) were 63.5% (95% CI 47.7-79.4) and 53.7% (95% CI, 38.9-68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1-year PFS 67.2% (95% CI 51.9-82.4) versus 15.0% (95% CI 0-40.2), p < .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR-T therapy is effective in treating R/R T-ALL/LBL patients with promising PFS while maintaining a manageable safety profile.© 2023 Wiley Periodicals LLC.