OBJECTIVE We conducted a first-in-human study to evaluate the bioactivity and safety of B7-H3-targeted chimeric antigen receptor (CAR) autologous T cells for treating recurrent anaplastic meningioma. METHODS Tumor tissues from a patient with recurrent anaplastic meningioma were evaluated for B7-H3 expression. B7-H3-targeted CAR-T cells were delivered into the intracranial tumor resection cavity using an Ommaya device at a maximum dose of 1.5 × 107 cells. Magnetic resonance imaging (MRI) screening and multiple serum indexes were regularly monitored. The patient received surgical intervention after three-cycle infusions, allowing analysis for CAR-T-cell infiltration and target antigen expression in post-CAR-T therapy tumor tissues. RESULTS Immunochemical analysis demonstrated high and homogeneous B7-H3 expression in tumor samples. MRI results indicated that the tumor near the delivery device was relatively stable compared with the rapid progression of tumors distant from the device. We found CAR-T-cell trafficking to regions of B7-H3+ tumor tissues near the device, but not to tumor tissues distant from the device. Decreased B7-H3 expression was observed near the region of CAR-T-cell infiltration after therapy. The intracavitary delivery of B7-H3-targeted CAR-T cells was well-tolerated and not associated with any toxic effects of grade 3 or higher. CONCLUSION Our results suggested that although intracavitary administration of B7-H3-targeted CAR-T cells was safe and resulted in local bioactivity, addressing antigen loss and CAR-T-cell trafficking may further enhance the applications of B7-H3-targeted CAR-T-cell therapy.

中文翻译：

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B7-H3靶向嵌合抗原受体T细胞对抗间变性脑膜瘤的生物活性和安全性。

目的：我们进行了一项首次人体研究，以评估 B7-H3 靶向嵌合抗原受体 (CAR) 自体 T 细胞治疗复发性间变性脑膜瘤的生物活性和安全性。方法 评估来自复发性间变性脑膜瘤患者的肿瘤组织的 B7-H3 表达。使用 Ommaya 装置以 1.5 × 107 个细胞的最大剂量将 B7-H3 靶向 CAR-T 细胞递送到颅内肿瘤切除腔中。定期监测磁共振成像（MRI）筛查和多种血清指标。患者在三周期输注后接受了手术干预，从而可以分析 CAR-T 细胞浸润和 CAR-T 治疗后肿瘤组织中的靶抗原表达。结果 免疫化学分析显示肿瘤样本中 B7-H3 高且均一的表达。MRI结果表明，与远离装置的肿瘤快速进展相比，递送装置附近的肿瘤相对稳定。我们发现 CAR-T 细胞运输到设备附近的 B7-H3+ 肿瘤组织区域，但没有运输到远离设备的肿瘤组织。治疗后在 CAR-T 细胞浸润区域附近观察到 B7-H3 表达降低。B7-H3靶向CAR-T细胞的腔内递送具有良好的耐受性，并且与3级或更高级别的任何毒性作用无关。结-细胞疗法。