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

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

doi:https://doi.org/10.1007/s00262-024-03808-0

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

Tachi, Tetsuro; Kijima, Noriyuki; Kuroda, Hideki et al.

Cancer Immunology, Immunotherapy, 2024, 73(256)

Number of Access:76（2025-05-02 15:37 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98912

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Title	Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model
Creator	researchmap permalink tetsu218 tetsu218 CreatorName Tachi, Tetsuro
	NRID 1000080534627 1000080534627 researchmap permalink kiji kiji Scopus Author ID 53463724600 53463724600 ORCID 0000-0003-2103-1909 0000-0003-2103-1909 CreatorName Kijima, Noriyuki
	researchmap permalink kurodahideki kurodahideki CreatorName Kuroda, Hideki
	researchmap permalink ishunya ishunya CreatorName Ikeda, Syunya
	CreatorName Murakami, Koki
	NRID 1000060837946 1000060837946 CreatorName Nakagawa, Tomoyoshi
	CreatorName Yaga, Moto
	CreatorName Nakagawa, Kanji
	researchmap permalink r1990 r1990 CreatorName Utsugi, Reina
	NRID 1000020593734 1000020593734 ORCID 0000-0002-3739-6219 0000-0002-3739-6219 researchmap permalink rhirayama rhirayama Scopus Author ID 37034068100 37034068100 CreatorName Hirayama, Ryuichi
	NRID 1000010533797 1000010533797 researchmap permalink yoshiko_okita yoshiko_okita Scopus Author ID 14007410000 14007410000 CreatorName Okita, Yoshiko
	NRID 1000050444542 1000050444542 researchmap permalink naokikagawa naokikagawa Scopus Author ID 8945727800 8945727800 ORCID 0000-0002-0674-2342 0000-0002-0674-2342 CreatorName Kagawa, Naoki
	NRID 1000010332743 1000010332743 researchmap permalink hkishima hkishima Scopus Author ID 6603783358 6603783358 ORCID 0000-0002-9041-2337 0000-0002-9041-2337 CreatorName Kishima, Haruhiko
	NRID 1000090419284 1000090419284 CreatorName Imai, Chihaya
	NRID 1000010456923 1000010456923 researchmap permalink hnaoki hnaoki Scopus Author ID 55928728700 55928728700 ORCID 0000-0001-9570-0947 0000-0001-9570-0947 CreatorName Hosen, Naoki
Subject	Antitumor effect
	B7-H3
	CAR-NK cell therapy
	Glioblastoma (GBM)
Description	The version of record of this article, first published in Cancer Immunology, Immunotherapy, is available online at Publisher’s website: https://doi.org/10.1007/s00262-024-03808-0.
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.
Publisher	Springer Science and Business Media Deutschland GmbH
Source Title	Cancer Immunology, Immunotherapy
Volume (Issue)	73(256)
Date of Issued	2024-10-05
Language	English
Handle URL	https://hdl.handle.net/11094/98912
PISSN	03407004
eISSN	14320851
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s00262-024-03808-0
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Cancer Immunology, Immunotherapy. 2024, 73(256)
DC.title	Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model
DC.creator	Tachi, Tetsuro
	Kijima, Noriyuki
	Kuroda, Hideki
	Ikeda, Syunya
	Murakami, Koki
	Nakagawa, Tomoyoshi
	Yaga, Moto
	Nakagawa, Kanji
	Utsugi, Reina
	Hirayama, Ryuichi
	Okita, Yoshiko
	Kagawa, Naoki
	Kishima, Haruhiko
	Imai, Chihaya
	Hosen, Naoki
DC.publisher	Springer Science and Business Media Deutschland GmbH
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-10-05
DC.identifier	https://doi.org/10.1007/s00262-024-03808-0
DC.subject	Antitumor effect
	B7-H3
	CAR-NK cell therapy
	Glioblastoma (GBM)
DC.description	The version of record of this article, first published in Cancer Immunology, Immunotherapy, is available online at Publisher’s website: https://doi.org/10.1007/s00262-024-03808-0.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98912
citation_title	Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model
citation_author	Tachi, Tetsuro
	Kijima, Noriyuki
	Kuroda, Hideki
	Ikeda, Syunya
	Murakami, Koki
	Nakagawa, Tomoyoshi
	Yaga, Moto
	Nakagawa, Kanji
	Utsugi, Reina
	Hirayama, Ryuichi
	Okita, Yoshiko
	Kagawa, Naoki
	Kishima, Haruhiko
	Imai, Chihaya
	Hosen, Naoki
citation_publisher	Springer Science and Business Media Deutschland GmbH
citation_language	English
citation_date	2024-10-05
citation_journal_title	Cancer Immunology, Immunotherapy
citation_volume	73
citation_issue	256
citation_doi	https://doi.org/10.1007/s00262-024-03808-0
citation_public_url	https://hdl.handle.net/11094/98912

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

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