颅内注射 B7-H3 靶向 Car-T 和 Car-NK 细胞在患者来源的胶质母细胞瘤异种移植模型中的抗肿瘤作用。
Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.
机构信息
Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.
World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
出版信息
Cancer Immunol Immunother. 2024 Oct 5;73(12):256. doi: 10.1007/s00262-024-03808-0.
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.
背景
多形性胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤，需要新的治疗方法。最近，嵌合抗原受体（CAR）T 细胞疗法已被证明对 GBM 有效，但它是一种个性化药物，细胞生产需要高成本和长时间。CAR 转导的自然杀伤（NK）细胞可用于“现货”细胞免疫疗法，因为它们不会引起移植物抗宿主病。因此，我们旨在分析针对 B7-H3 的 CAR-T 或 NK 细胞对 GBM 的抗作用，因为已知 B7-H3 在 GBM 中高度表达。
方法
使用先前报道的抗 B7-H3 scFv 序列生成针对 B7-H3 的 CAR-T 细胞。还生成了转导 B7-H3 CAR 的脐血（CB）衍生 NK 细胞。在体外分析了它们的抗 GBM 作用。在携带患者来源的 GBM 细胞的体内异种移植模型中研究了 B7-H3 CAR-T 或 NK 细胞颅内注射的抗肿瘤作用。
结果
B7-H3 CAR-T 细胞和 CAR-NK 细胞在体外均对患者来源的 GBM 细胞表现出明显的细胞毒性。此外，针对 B7-H3 的 CAR-T 细胞和 CAR-NK 细胞颅内注射对患者来源的 GBM 异种移植物具有显著的抗肿瘤作用。
结论
不仅 CAR-T 细胞，而且针对 B7-H3 的 CB 衍生 CAR-NK 细胞都有可能消除 GBM 细胞。
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