撰稿 | 张海伟 责编 | 周叶斌 GD2蛋白在几乎所有的神经母细胞瘤和80%的骨肉瘤上均有高表达，是抗体依赖性细胞毒性类药物的靶点。目前已有抗GD2单克隆抗体在临床应用，但有10%-20%的高危神经母细胞瘤患者未能获得缓解，50%-60%的干细胞移植后接受免疫治疗的患者出现复发。因此用携带抗CD3和抗GD2双特异性抗体（GD2Bi）的自体T活化细胞（GD2BATs）靶向神经母细胞瘤和骨肉瘤可能是一种可行有效的方法。近日，来自美国的 Maxim Yankelevich 和 Nai-Kong V Cheung 等组成的研究团队，在Journal for the immunotherapy of Cancer 发表题为 Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells 的文章，展示在美国多个儿童医院和儿科中心开展临床研究评价GD2BATs安全性和疗效的结果。
Background: The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.Methods: The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×106 GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m2) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m2). The phase II segment focused on patients with NB at the dose 3 level of 160×106 GD2BATs/kg/infusion.Results: Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2-3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines.DOI: 10.1136/jitc-2023-008744👇点击此处，直达原文
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