美国贝勒医学院Leonid S. Metelitsa、Andras Heczey等研究人员合作发现，抗GD2的CAR-NKT细胞可用于复发性或难治性神经母细胞瘤患者。这一研究成果于2020年10月22日在线发表在国际学术期刊《自然—医学》上。

研究人员报告了在复发或耐药的儿童神经母细胞瘤的自发性自然杀伤T细胞（NKT）1期剂量递增试验中，以剂量水平1入组的所有三名患者的中期结果，这些NKT细胞经工程设计可共表达GD2特异性嵌合抗原受体（CAR）以及白细胞介素15（NCT03294954）。主要和次要目标分别是评估安全性和抗肿瘤反应，并将免疫反应评估作为附加目标。

研究人员离体扩增了高纯度的NKT细胞（平均值±标准差，94.7±3.8％），并在用环磷酰胺/氟达拉滨（Cy/Flu）进行淋巴结消除后，每平方米体表面积用3×10⁶个CAR-NKT细胞治疗了患者。Cy/Flu处理可能是造成3–4级血液学不良事件的原因，因为它们发生在输注CAR-NKT细胞之前，并且未观察到剂量限制性毒性。CAR-NKT细胞在体内扩增，定位于肿瘤，并且在一名患者中诱导了客观的反应，使骨转移性病变消退。

这些初步结果表明，CAR-NKT细胞可以扩展到临床规模，并可以安全地用于治疗癌症患者。

据了解，在鼠肿瘤模型中，Vα24恒定NKT已显示出强大的抗肿瘤特性，并与癌症患者的良好预后相关。但是，人类中这些细胞的数量很少，阻碍了它们的临床应用。

附：英文原文

Title: Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis

Author: Andras Heczey, Amy N. Courtney, Antonino Montalbano, Simon Robinson, Ka Liu, Mingmei Li, Nisha Ghatwai, Olga Dakhova, Bin Liu, Tali Raveh-Sadka, Cynthia N. Chauvin-Fleurence, Xin Xu, Ho Ngai, Erica J. Di Pierro, Barbara Savoldo, Gianpietro Dotti, Leonid S. Metelitsa

Issue&Volume: 2020-10-12

Abstract: Vα24-invariant natural killer T (NKT) cells have shown potent anti-tumor properties in murine tumor models and have been linked to favorable outcomes in patients with cancer. However, low numbers of these cells in humans have hindered their clinical applications. Here we report interim results from all three patients enrolled on dose level 1 in a phase 1 dose-escalation trial of autologous NKT cells engineered to co-express a GD2-specific chimeric antigen receptor (CAR) with interleukin-15 in children with relapsed or resistant neuroblastoma (NCT03294954). Primary and secondary objectives were to assess safety and anti-tumor responses, respectively, with immune response evaluation as an additional objective. We ex vivo expanded highly pure NKT cells (mean ± s.d., 94.7 ± 3.8%) and treated patients with 3 × 106 CAR-NKT cells per square meter of body surface area after lymphodepleting conditioning with cyclophosphamide/fludarabine (Cy/Flu). Cy/Flu conditioning was the probable cause for grade 3–4 hematologic adverse events, as they occurred before CAR-NKT cell infusion, and no dose-limiting toxicities were observed. CAR-NKT cells expanded in vivo, localized to tumors and, in one patient, induced an objective response with regression of bone metastatic lesions. These initial results suggest that CAR-NKT cells can be expanded to clinical scale and safely applied to treat patients with cancer.

DOI: 10.1038/s41591-020-1074-2

Source: https://www.nature.com/articles/s41591-020-1074-2