GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas

脑脊液 医学 毒性 胶质瘤 癌症研究 脊髓 中枢神经系统 内科学 精神科
作者
Robbie G. Majzner,Sneha Ramakrishna,Kristen W. Yeom,Shabnum Patel,Harshini Chinnasamy,Liora M. Schultz,Rebecca M. Richards,Li Jiang,Valentin Barsan,Rebecca Mancusi,Anna C. Geraghty,Zinaida Good,Aaron Mochizuki,Shawn Gillespie,Angus Toland,Jasia Mahdi,Agnes Reschke,Esther H. Nie,Isabelle J. Chau,Maria Caterina Rotiroti,Christopher W. Mount,Christina Baggott,Sharon Mavroukakis,Emily Egeler,Jennifer Moon,Courtney Erickson,Sean Green,Michael Kunicki,Michelle Fujimoto,Zachary Ehlinger,Warren D. Reynolds,Sreevidya Kurra,Katherine E. Warren,Snehit Prabhu,Hannes Vogel,Lindsey Rasmussen,Timothy T. Cornell,Sonia Partap,Paul G. Fisher,Cynthia J. Campen,Mariella G. Filbin,Gerald A. Grant,Bita Sahaf,Kara L. Davis,Steven A. Feldman,Crystal L. Mackall,Michelle Monje
出处
期刊:Nature [Nature Portfolio]
卷期号:603 (7903): 934-941 被引量:533
标识
DOI:10.1038/s41586-022-04489-4
摘要

Abstract Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system 1 . We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells 2 , providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 10 6 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly 3 . Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
SYLH应助科研通管家采纳,获得10
刚刚
深情安青应助科研通管家采纳,获得10
刚刚
郑方形发布了新的文献求助20
刚刚
英俊的铭应助科研通管家采纳,获得10
刚刚
SYLH应助科研通管家采纳,获得20
刚刚
酷波er应助科研通管家采纳,获得10
刚刚
Akim应助科研通管家采纳,获得10
刚刚
斯文败类应助科研通管家采纳,获得10
刚刚
MchemG应助科研通管家采纳,获得10
1秒前
英俊的铭应助科研通管家采纳,获得10
1秒前
CAOHOU应助科研通管家采纳,获得10
1秒前
1秒前
1秒前
2秒前
爱撞墙的猫完成签到,获得积分10
2秒前
小马甲应助干雅柏采纳,获得10
2秒前
小晓完成签到,获得积分10
2秒前
becky发布了新的文献求助10
3秒前
jszhoucl发布了新的文献求助10
4秒前
星期八发布了新的文献求助10
4秒前
时有落花至完成签到,获得积分10
4秒前
4秒前
无与伦比发布了新的文献求助30
8秒前
10秒前
一人独钓一江秋完成签到,获得积分10
10秒前
12秒前
13秒前
干雅柏发布了新的文献求助10
15秒前
搜集达人应助俏皮芷蕊采纳,获得10
17秒前
上官若男应助sugar采纳,获得10
18秒前
xxxllllll发布了新的文献求助30
18秒前
18秒前
CodeCraft应助wangqiuhong采纳,获得10
19秒前
21秒前
桐桐应助jszhoucl采纳,获得10
21秒前
黄健斌完成签到,获得积分10
22秒前
HarryChan完成签到,获得积分10
24秒前
27秒前
28秒前
28秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989444
求助须知:如何正确求助?哪些是违规求助? 3531531
关于积分的说明 11254250
捐赠科研通 3270191
什么是DOI,文献DOI怎么找? 1804901
邀请新用户注册赠送积分活动 882105
科研通“疑难数据库(出版商)”最低求助积分说明 809174