Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial.
Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial.
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在I/II期临床试验中，图像引导的嵌合抗原受体（CAR）T细胞的介入放射学递送用于胸膜恶性肿瘤。
DOI：
10.1016/j.lungcan.2022.01.003
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发表时间：
2022-03
期刊：
影响因子：
5.3
通讯作者：
Solomon, Stephen B.
中科院分区：
文献类型：
--
作者：
Ghosn, Mario;Cheema, Waseem;Zhu, Amy;Livschitz, Jennifer;Maybody, Majid;Boas, Franz E.;Santos, Ernesto;Kim, DaeHee;Beattie, Jason A.;Offin, Michael;Rusch, Valerie W.;Zauderer, Marjorie G.;Adusumilli, Prasad S.;Solomon, Stephen B.
关键词：
我们描述了 I/II 期试验中在胸膜恶性肿瘤患者中进行图像引导递送间皮素靶向嵌合抗原受体 (CAR) T 细胞的技术和结果 (ClinicalTrials.gov: NCT02414269)。没有胸膜导管或缺乏插入导管积液的患者（41 名中的 31 名）由介入放射科医生在计算机断层扫描或超声图像引导下进行胸膜内 CAR T 细胞注射。 CAR T 细胞通过针头注入可触及的胸膜腔（腔内）或在诱导的腔内人工气胸后进行注射。对于腔内输注不可行的患者，通过经皮方法在胸膜结节/增厚部位（瘤内）周围和/或内部注射 CAR T 细胞。评估手术前和手术后的临床、实验室和影像学结果。对 31 名患者进行了胸腔内注射 CAR T 细胞（33 次手术，2 名患者接受了第二剂），并成功交付了计划剂量（10-186 mL）； 14/33 (42%) 腔内和 19/33 (58%) 瘤内。所有程序均在 T 细胞解冻后 2 小时内完成。没有发生大于 1 级的手术相关不良事件（三分之一的患者之前接受过同侧胸膜融合手术）。最常见的影像学表现是毛玻璃样混浊伴小叶间隔增厚和/或实变，在 12/33 (36%) 的手术中观察到。不同输注方法之间的发热发生率、CRP、IL-6和外周血载体拷贝数峰值没有差异。使用腔内或瘤内途径进行图像引导的 CAR T 细胞胸膜内递送对于解剖结构可变的胸膜癌是可行的、可重复的且安全的。
We describe techniques and results of image-guided delivery of mesothelin-targeted chimeric antigen receptor (CAR) T cells in patients with pleural malignancies in a phase I/II trial (ClinicalTrials.gov: NCT02414269). Patients without a pleural catheter or who lack effusion for insertion of a catheter (31 of 41) were administered intrapleural CAR T cells by interventional radiologists under image guidance by computed tomography or ultrasound. CAR T cells were administered through a needle in an accessible pleural loculation (intracavitary) or following an induced loculated artificial pneumothorax. In patients where intracavitary infusion was not feasible, CAR T cells were injected via percutaneous approach either surrounding and/or in the pleural nodule/thickening (intratumoral). Pre- and post-procedural clinical, laboratory, and imaging findings were assessed. CAR T cells were administered intrapleurally in 31 patients (33 procedures, 2 patients were administered a second dose) with successful delivery of planned dose (10–186 mL); 14/33 (42%) intracavitary and 19/33 (58%) intratumoral. All procedures were completed within 2 hours of T-cell thawing. There were no procedure-related adverse events greater than grade 1 (1 in 3 patients had prior ipsilateral pleural fusion procedures). The most common imaging finding was ground glass opacities with interlobular septal thickening and/or consolidation, observed in 12/33 (36%) procedures. There was no difference in the incidence of fever, CRP, IL-6, and peak vector copy number in the peripheral blood between infusion methods. Image-guided intrapleural delivery of CAR T cells using intracavitary or intratumoral routes is feasible, repeatable and safe across anatomically variable pleural cancers.
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