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PSMA嵌合抗原受体T细胞(CAR-T)联合GD2 CAR-T治疗难治性/复发性胶质瘤的初步探索

Preliminary exploration of PSMA CAR-T combined with GD2 CAR-T for the treatment of refractory/relapsed gliomas.

作者信息

Gu Jinshan, Li Jiasheng, Xu Yang, Zhang Ge, Xie Jingyi, Jia Rui, Chen Wei, Lu Zhengfeng, Chang Chengwei, Wen Haijun, Chang Lung-Ji, Ma Huajuan, Cai Qichun

机构信息

Immuno-oncology department of the cancer center, 21 st Floor, Building 2, Guangdong Clifford Hospital, Hongfu Road, Panyu District, Guangzhou, 511400, China.

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.

出版信息

J Transl Med. 2025 May 27;23(1):591. doi: 10.1186/s12967-025-06523-1.

Abstract

BACKGROUND

This study aimed to investigate the safety and efficacy of fourth-generation combined PSMA and GD2-targeted chimeric antigen receptor (CAR)-T cells in the treatment of refractory/relapsed gliomas.

METHOD

This study employed a single-arm design, enrolling patients with confirmed refractory/relapsed gliomas at the Immuno-oncology Department of the Cancer Center at Clifford Hospital in Guangdong. Eligible patients received combined treatment with PSMA CAR-T and GD2 CAR-T cells via intravenous administration. The dose of reinfused CAR-T cells ranged from 1-5 × 10^6 cells/kg of body weight.

RESULTS

Six patients were included in the study, all of whom responded to the treatment. The overall response rate (ORR) was 50%, with three patients achieving complete response (CR) (50%) and three demonstrating stable disease (SD) (50%). The median progression-free survival (PFS) was 9.0 months (range, 1-56 months), and the median overall survival (OS) was 24.5 months (range, 13-63 months). Three patients (50%) developed cytokine release syndrome (CRS), all of which were classified as grade I CRS, and no patients experienced immune effector cell-associated neurotoxicity Syndrome (ICANS).

CONCLUSION

Combined PSMA CAR-T and GD2 CAR-T cell therapy demonstrated significant efficacy and good tolerability in the treatment of refractory/relapsed gliomas, without severe adverse reactions.

摘要

背景

本研究旨在探讨第四代联合靶向前列腺特异性膜抗原(PSMA)和神经节苷脂2(GD2)的嵌合抗原受体(CAR)-T细胞治疗难治性/复发性胶质瘤的安全性和有效性。

方法

本研究采用单臂设计,纳入广东祈福医院癌症中心免疫肿瘤科确诊的难治性/复发性胶质瘤患者。符合条件的患者通过静脉注射接受PSMA CAR-T和GD2 CAR-T细胞联合治疗。回输的CAR-T细胞剂量为1-5×10^6个细胞/千克体重。

结果

6例患者纳入研究,所有患者均对治疗有反应。总缓解率(ORR)为50%,3例患者达到完全缓解(CR)(50%),3例病情稳定(SD)(50%)。无进展生存期(PFS)中位数为9.0个月(范围1-56个月),总生存期(OS)中位数为24.5个月(范围13-63个月)。3例患者(50%)发生细胞因子释放综合征(CRS),均为I级CRS,无患者发生免疫效应细胞相关神经毒性综合征(ICANS)。

结论

PSMA CAR-T和GD2 CAR-T细胞联合疗法在治疗难治性/复发性胶质瘤中显示出显著疗效和良好耐受性,且无严重不良反应。

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