Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial
Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial
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表达 CD30 嵌合抗原受体的自体 T 细胞治疗复发或难治性霍奇金淋巴瘤：开放标签 I 期试验
DOI：
10.1158/1078-0432.ccr-16-1365
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发表时间：
2017-03-01
影响因子：
11.5
通讯作者：
Han, Wei-Dong
中科院分区：
文献类型：
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作者：
Wang, Chun-Meng;Wu, Zhi-Qiang;Han, Wei-Dong
目的：复发或难治性的霍奇金淋巴瘤是医学肿瘤学家的挑战，因为总体生存率差。我们的目的是评估CD30靶向CAR T细胞在进行性复发或难治性Hodgkin淋巴瘤患者中的可行性，安全性和功效。实验性设计：患有复发或难治性Hodgkin淋巴瘤的患者接受了调节性化学疗法，随后接受了Cart-30细胞输注。 。根据定量PCR（QPCR）定期测量外周血和活检肿瘤组织中的CAR转基因水平。分辨率：招募了18名患者；大多数人患有较重的治疗史或多个肿瘤病变，并在输注过程中平均每公斤（SD，0.25;范围，1.1-2.1）的平均每公斤CAR阳性T细胞（范围为1.1-2.1）。 CART-30细胞输注的耐受性，> = 3级毒性仅发生在18例患者中的两名中。在18例患者中，有7例已达到部分缓解，有6例达到了稳定的疾病。观察到淋巴瘤不一致的反应：淋巴结比外道路外病变更好，肺部病变的反应似乎相对较差。淋巴细胞的恢复伴随着循环CAR T细胞的增加（输注后3至9天之间的峰值）是临床反应的可能的起诉者。通过qPCR和免疫组织化学对活检组织的分析表明，肿瘤中的CAR T细胞向靶向部位进行了运输，并减少CD30的表达。结论：CART-30细胞治疗是安全的，可行的，可行的，并且有效地在复发或顽固性淋巴瘤和保证中大规模的患者招募。 （c）2016 AACR。
Purpose: Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin lymphoma. Experimental Design: Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR). Results: Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 107 CAR-positive T cell per kg (SD, 0.25; range, 1.1–2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors. Conclusions: CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment. Clin Cancer Res; 23(5); 1156–66. ©2016 AACR.