近日，美国宾夕法尼亚大学Carl H. June团队研究了增强CAR-T细胞治疗先前治疗失败的淋巴瘤的疗效。相关论文于2025年5月8日发表在《新英格兰医学杂志》上。

靶向CD19的嵌合抗原受体（CAR） T细胞已经改变了B细胞癌的治疗方法，但许多患者没有长期缓解。该研究团队设计了一种抗CD19增强CAR-T细胞产品（huCART19-IL18），它分泌白细胞介素-18来增强抗肿瘤活性。

研究组评估了huCART19-IL18在既往抗CD19 CAR-T细胞治疗后复发或难治性淋巴瘤患者中的安全性、可行性和初步疗效。使用3天的制造过程，研究团队以3×10⁶至3×10⁸的剂量给药huCART19-IL18阳性细胞。

共有21例患者接受了huCART19-IL18治疗。62%的患者发生细胞因子释放综合征（47%为1级或2级），14%的患者发生免疫效应细胞相关神经毒性综合征（均为1级或2级）。未观察到意外不良事件。在所有剂量水平下均检测到稳健的CAR-T细胞扩增。在输注后3个月，81%的患者出现完全或部分缓解（90%置信区间，62 - 93），52%的患者出现完全缓解（90%置信区间，33 - 71）。中位随访时间为17.5个月（范围3 - 34），中位缓解持续时间为9.6个月（90% CI， 5.5 -未达到）。

研究结果表明，在这项小型研究中，huCART19-IL18具有与其他CAR-T细胞治疗一致的安全性，并且在先前抗CD19 CAR-T细胞治疗失败后，以低细胞剂量治疗淋巴瘤患者显示出颇有前景的疗效。

附：英文原文

Title: Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure

Author: Jakub Svoboda, Daniel J. Landsburg, James Gerson, Sunita D. Nasta, Stefan K. Barta, Elise A. Chong, Michael Cook, Noelle V. Frey, Joanne Shea, Amanda Cervini, Amy Marshall, Megan Four, Megan M. Davis, Julie K. Jadlowsky, Anne Chew, Edward Pequignot, Vanessa Gonzalez, Julia Han Noll, Luca Paruzzo, Juliana Rojas-Levine, Gabriela Plesa, John Scholler, Donald L. Siegel, Bruce L. Levine, David L. Porter, Saba Ghassemi, Marco Ruella, Andrew Rech, Rachel M. Leskowitz, Joseph A. Fraietta, Wei-Ting Hwang, Elizabeth Hexner, Stephen J. Schuster, Carl H. June

Issue&Volume: 2025-05-08

Abstract:

BACKGROUND

Chimeric antigen receptor (CAR) T cells targeting CD19 have transformed the treatment of B-cell cancers, but many patients do not have long-term remission. We designed an anti-CD19 enhanced (armored) CAR T-cell product (huCART19-IL18) that secretes interleukin-18 to enhance antitumor activity.

METHODS

In this study, we assessed the safety, feasibility, and preliminary efficacy of huCART19-IL18 in patients with relapsed or refractory lymphoma after previous anti-CD19 CAR T-cell therapy. Using a 3-day manufacturing process, we administered huCART19-IL18–positive cells in doses ranging from 3×106 to 3×108.

RESULTS

A total of 21 patients received huCART19-IL18. Cytokine release syndrome occurred in 62% of the patients (47% with grade 1 or 2), and immune effector-cell–associated neurotoxicity syndrome occurred in 14% (all grade 1 or 2). No unexpected adverse events were observed. Robust CAR T-cell expansion was detected across all dose levels. At 3 months after infusion, a complete or partial response was seen in 81% of the patients (90% confidence interval [CI], 62 to 93) and a complete response in 52% (90% CI, 33 to 71). With a median follow-up of 17.5 months (range, 3 to 34), the median duration of response was 9.6 months (90% CI, 5.5 to not reached).

CONCLUSIONS

In this small study, huCART19-IL18 had a safety profile consistent with other CAR T-cell treatments and showed promising efficacy at low cell doses in patients with lymphoma after the failure of previous anti-CD19 CAR T-cell therapy.

DOI: NJ202505083921809

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2408771