肿瘤细胞治疗研究
英文原题：Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.
不仅 CAR-T 细胞，靶向 B7-H3 的 CB 来源 CAR-NK 细胞也可能具有消除 GBM 细胞的潜力。
背景：多形性胶质母细胞瘤（GBM）是致死率最高的原发性脑肿瘤，亟需新疗法。近期研究显示，嵌合抗原受体（CAR）T 细胞治疗对 GBM 有效，但这是一种个体化医疗方式，细胞制备成本高、耗时长。CAR 转导的自然杀伤（NK）细胞不会诱发移植物抗宿主病，因此可作为“现成型”细胞免疫疗法。鉴于 B7-H3 在 GBM 中高表达，本研究旨在分析靶向 B7-H3 的 CAR-T 或 CAR-NK 细胞的抗 GBM 效果。方法：根据既往报道的抗 B7-H3 单链可变片段序列制备靶向 B7-H3 的 CAR-T 细胞，并制备经 B7-H3 CAR 转导的脐带血（CB）来源 NK 细胞。在体外分析其抗 GBM 效果；在患者来源 GBM 细胞异种移植体内模型中，研究颅内注射 B7-H3 CAR-T 或 CAR-NK 细胞的抗肿瘤作用。结果：B7-H3 CAR-T 细胞和 CAR-NK 细胞在体外均能显著杀伤患者来源的 GBM 细胞。此外，颅内注射靶向 B7-H3 的 CAR-T 或 CAR-NK 细胞，可显著抑制患者来源 GBM 异种移植瘤。结论：靶向 B7-H3 的 CAR-T 细胞和脐带血来源 CAR-NK 细胞均可能清除 GBM 细胞。
BACKGROUND: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor for which novel therapies are needed. Recently, chimeric antigen receptor (CAR) T cell therapy has been shown to be effective against GBM, but it is a personalized medicine and requires high cost and long time for the cell production. CAR-transduced natural killer (NK) cells can be used for "off-the-shelf" cellular immunotherapy because they do not induce graft-versus-host disease. Therefore, we aimed to analyze the anti-GBM effect of CAR-T or NK cells targeting B7-H3, which is known to be highly expressed in GBM. METHODS: CAR-T cells targeting B7-H3 were generated using previously reported anti-B7-H3 scFv sequences. Cord blood (CB)-derived NK cells transduced with the B7-H3 CAR were also generated. Their anti-GBM effect was analyzed in vitro. The antitumor effect of intracranial injection of the B7-H3 CAR-T or NK cells was investigated in an in vivo xenograft model with patient-derived GBM cells. RESULTS: Both B7-H3 CAR-T cells and CAR-NK cells exhibited marked cytotoxicity against patient-derived GBM cells in vitro. Furthermore, intracranial injection of CAR-T cells and CAR-NK cells targeting B7-H3 resulted in a significant antitumor effect against patient-derived GBM xenografts. CONCLUSION: Not only CAR-T cells but also CB-derived CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells.
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