CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
靶向氯毒素的 CAR-T 细胞治疗复发性胶质母细胞瘤：证明可行性与安全性的中期临床经验
英文原题：Chlorotoxin-directed CAR T cell therapy for recurrent glioblastoma: Interim clinical experience demonstrating feasibility and safety.
查看英文原题
Chlorotoxin-directed CAR T cell therapy for recurrent glioblastoma: Interim clinical experience demonstrating feasibility and safety.
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中文摘要
胶质母细胞瘤（GBM）治疗的一项挑战是患者间及肿瘤内部的表型异质性。蝎毒中的多肽氯毒素（CLTX）可通过涉及细胞表面基质金属蛋白酶-2（MMP-2）的机制广泛结合胶质瘤细胞。研究者此前开发了将 CLTX 作为 GBM 识别结构域的 CAR-T 细胞。本文报告一项 I 期试验的中期临床结果：4 例 MMP-2 表达型复发 GBM 患者接受腔内/瘤内（ICT）CLTX-CAR-T 给药（NCT04214392），主要目标是评估可行性和安全性。该疗法耐受性良好，未出现剂量限制性毒性。4 名参与者中 3 名（75%）最佳疗效为疾病稳定。肿瘤腔液中可检测到 CLTX-CAR-T 细胞，血液中检测水平较低。人抗 CAR 抗体检测未发现针对 CLTX-CAR 的体液免疫原性。这些观察结果支持进一步开展 CLTX-CAR 治疗的临床评估。
展开英文摘要原文
A challenge in treating glioblastoma (GBM) is its phenotypic heterogeneity between patients and within tumors. Chlorotoxin (CLTX), a peptide from scorpion venom, broadly binds glioma cells through a mechanism involving surface matrix metalloproteinase-2 (MMP-2).
We previously developed chimeric antigen receptor (CAR) T cells incorporating CLTX as the GBM recognition domain.
Here, we report interim clinical experience of a phase 1 trial evaluating intracavity/intratumoral (ICT) delivery of CLTX-CAR T cells in four patients with MMP-2-expressing recurrent GBM (NCT04214392), with the primary objectives of feasibility and safety. The therapy is well tolerated with no dose-limiting toxicities.
Three of the four participants (75%) exhibit a best response of stable disease. CLTX-CAR T cells are detected in the tumor cavity fluid and at lower levels in the blood. Human anti-CAR antibody assays do not detect humoral immunogenicity against the CLTX-CAR. These observations support further clinical evaluation of CLTX-CAR therapy.
论文信息
- 作者
- Barish ME、Aftabizadeh M、Hibbard J、Blanchard MS、Ostberg JR、Wagner JR、Manchanda M、Paul J
- 第一作者单位
- Department of Stem Cell Biology & Regenerative Medicine, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.United States
- 通讯作者单位
- Division of Neurosurgery, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA. Electronic address: bbadie@coh.org.United States
- 文献类型
- I 期临床试验
- 期刊
- Cell reports. Medicine2025 Aug 19
- 原文标识
- PubMed 40818458 · DOI 10.1016/j.xcrm.2025.102302
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