Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.

IF 4.6 2区医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-10-05 DOI:10.1007/s00262-024-03808-0

Tetsuro Tachi, Noriyuki Kijima, Hideki Kuroda, Syunya Ikeda, Koki Murakami, Tomoyoshi Nakagawa, Moto Yaga, Kanji Nakagawa, Reina Utsugi, Ryuichi Hirayama, Yoshiko Okita, Naoki Kagawa, Haruhiko Kishima, Chihaya Imai, Naoki Hosen

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Abstract

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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颅内注射 B7-H3 靶向 Car-T 和 Car-Nk 细胞对患者来源胶质母细胞瘤异种移植模型的抗肿瘤作用。

背景：多形性胶质母细胞瘤（GBM多形性胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤，需要新型疗法来治疗。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，需要高成本和长时间的细胞生产。CAR转化的自然杀伤（NK）细胞可用于 "现成的 "细胞免疫疗法，因为它们不会诱发移植物抗宿主疾病。因此，我们旨在分析以B7-H3为靶点的CAR-T或NK细胞的抗GBM效果，已知B7-H3在GBM中高度表达：方法：使用之前报道的抗 B7-H3 scFv 序列生成靶向 B7-H3 的 CAR-T 细胞。方法：利用之前报道的抗 B7-H3 scFv 序列生成了靶向 B7-H3 的 CAR-T 细胞，同时还生成了转导了 B7-H3 CAR 的脐带血（CB）衍生 NK 细胞。我们在体外分析了它们的抗骨髓肉瘤效果。在患者来源的GBM细胞体内异种移植模型中，研究了颅内注射B7-H3 CAR-T或NK细胞的抗肿瘤效果：结果：B7-H3 CAR-T细胞和CAR-NK细胞在体外对患者来源的GBM细胞均表现出明显的细胞毒性。此外，颅内注射靶向 B7-H3 的 CAR-T 细胞和 CAR-NK 细胞可对患者来源的 GBM 异种移植物产生显著的抗肿瘤效果：结论：不仅是 CAR-T 细胞，源自 CB 的靶向 B7-H3 的 CAR-NK 细胞也可能具有消灭 GBM 细胞的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Immunology, Immunotherapy 医学-免疫学

CiteScore

10.50

自引率

1.70%

发文量

207

审稿时长

1 months

期刊介绍： Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.