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

被引：6

作者：

Tachi, Tetsuro ^{[1
]}

Kijima, Noriyuki ^{[1
]}

Kuroda, Hideki ^{[1
]}

Ikeda, Syunya ^{[2
]}

Murakami, Koki ^{[1
]}

Nakagawa, Tomoyoshi ^{[1
]}

Yaga, Moto ^{[3
]}

Nakagawa, Kanji ^{[1
]}

Utsugi, Reina ^{[1
]}

Hirayama, Ryuichi ^{[1
]}

Okita, Yoshiko ^{[1
]}

Kagawa, Naoki ^{[1
]}

Kishima, Haruhiko ^{[1
]}

Imai, Chihaya ^{[5
]}

Hosen, Naoki ^{[2
,4
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Neurosurg, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[2] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Suita, Osaka, Japan

[3] Osaka Gen Hosp, Dept Resp Med, Osaka, Japan

[4] Osaka Univ, Grad Sch Med, Dept Hematol & Oncol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[5] Univ Toyama, Fac Med, Dept Pediat, Toyama, Japan

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2024年 / 73卷 / 12期

关键词：

Antitumor effect; CAR-NK cell therapy; Glioblastoma (GBM); B7-H3; CHIMERIC ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; TARGETING B7-H3; TUMORS; IMMUNOTHERAPY; PERSISTENCE;

D O I：

10.1007/s00262-024-03808-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundGlioblastoma 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.MethodsCAR-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.ResultsBoth 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.ConclusionNot only CAR-T cells but also CB-derived CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells.

引用

页数：10

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