Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma

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

doi:https://doi.org/10.1007/s00262-025-03979-4

Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma

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

Cancer Immunology, Immunotherapy, 2025, 74(4), 136

Number of Access:100（2025-05-19 09:40 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/101004

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Title	Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma
Creator	researchmap permalink kurodahideki kurodahideki CreatorName Kuroda, Hideki
	NRID 1000080534627 1000080534627 ORCID 0000-0003-2103-1909 0000-0003-2103-1909 researchmap permalink kiji kiji Scopus Author ID 53463724600 53463724600 CreatorName Kijima, Noriyuki
	researchmap permalink tetsu218 tetsu218 CreatorName Tachi, Tetsuro
	researchmap permalink ishunya ishunya CreatorName Ikeda, Shunya
	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 ORCID 0000-0002-0674-2342 0000-0002-0674-2342 researchmap permalink naokikagawa naokikagawa Scopus Author ID 8945727800 8945727800 CreatorName Kagawa, Naoki
	NRID 1000010456923 1000010456923 ORCID 0000-0001-9570-0947 0000-0001-9570-0947 researchmap permalink hnaoki hnaoki Scopus Author ID 55928728700 55928728700 CreatorName Hosen, Naoki
	NRID 1000010332743 1000010332743 ORCID 0000-0002-9041-2337 0000-0002-9041-2337 researchmap permalink hkishima hkishima Scopus Author ID 6603783358 6603783358 CreatorName Kishima, Haruhiko
Subject	CAR-T cell therapy
	Expression cloning
	Glioblastoma (GBM)
	Monoclonal antibodies
	PTGFRN
Description	Kuroda H., Kijima N., Tachi T., et al. Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma. Cancer Immunology, Immunotherapy 74, 136 (2025); https://doi.org/10.1007/s00262-025-03979-4.
Abstract	Background: Chimeric antigen receptor (CAR)-T cell therapy targeting novel glioblastoma (GBM)-specific cell surface antigens is a promising approach. However, transcriptome analyses have revealed few GBM-specific target antigens. Methods: A library of monoclonal antibodies (mAbs) against tumor cell lines derived from patients with GBM was generated. mAbs reacting with tumor cells in resected tissues from patients with GBM but not with nonmalignant human brain cells were detected. The antigens that were recognized were identified through expression cloning. CAR-T cells derived from a candidate mAb were generated, and their functionality was tested in vitro and in vivo. Results: Approximately 3,200 clones were established. Among them, 5E17 reacted with tumor cells in six of seven patients with GBM, but not with nonmalignant human brain cells. Prostaglandin F2 receptor negative regulator (PTGFRN) was identified as an antigen recognized by 5E17. CAR-T cells derived from 5E17 produced cytokines and exerted cytotoxicity upon co-culture with tumor cells from patients with GBM. Furthermore, intracranial injection of 5E17-CAR-T cells demonstrated antitumor effects in an orthotopic xenograft murine model with patient-derived GBM cells. Conclusions: Cell surface PTGFRN is a candidate target for intracranial CAR-T cell therapy for GBM. On-target off-tumor toxicity in alternative normal tissues needs to be carefully tested.
Publisher	Springer Science and Business Media Deutschland GmbH
Source Title	Cancer Immunology, Immunotherapy
Volume (Issue)	74(4)
Page	136
Date of Issued	2025-03-06
Language	English
Handle URL	https://hdl.handle.net/11094/101004
PISSN	03407004
eISSN	14320851
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s00262-025-03979-4
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

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Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Cancer Immunology, Immunotherapy. 2025, 74(4), p. 136
DC.title	Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma
DC.creator	Kuroda, Hideki
	Kijima, Noriyuki
	Tachi, Tetsuro
	Ikeda, Shunya
	Murakami, Koki
	Nakagawa, Tomoyoshi
	Yaga, Moto
	Nakagawa, Kanji
	Utsugi, Reina
	Hirayama, Ryuichi
	Okita, Yoshiko
	Kagawa, Naoki
	Hosen, Naoki
	Kishima, Haruhiko
DC.publisher	Springer Science and Business Media Deutschland GmbH
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-03-06
DC.identifier	https://doi.org/10.1007/s00262-025-03979-4
DC.subject	CAR-T cell therapy
	Expression cloning
	Glioblastoma (GBM)
	Monoclonal antibodies
	PTGFRN
DC.description	Kuroda H., Kijima N., Tachi T., et al. Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma. Cancer Immunology, Immunotherapy 74, 136 (2025); https://doi.org/10.1007/s00262-025-03979-4.
DCTERMS.abstract	Background: Chimeric antigen receptor (CAR)-T cell therapy targeting novel glioblastoma (GBM)-specific cell surface antigens is a promising approach. However, transcriptome analyses have revealed few GBM-specific target antigens. Methods: A library of monoclonal antibodies (mAbs) against tumor cell lines derived from patients with GBM was generated. mAbs reacting with tumor cells in resected tissues from patients with GBM but not with nonmalignant human brain cells were detected. The antigens that were recognized were identified through expression cloning. CAR-T cells derived from a candidate mAb were generated, and their functionality was tested in vitro and in vivo. Results: Approximately 3,200 clones were established. Among them, 5E17 reacted with tumor cells in six of seven patients with GBM, but not with nonmalignant human brain cells. Prostaglandin F2 receptor negative regulator (PTGFRN) was identified as an antigen recognized by 5E17. CAR-T cells derived from 5E17 produced cytokines and exerted cytotoxicity upon co-culture with tumor cells from patients with GBM. Furthermore, intracranial injection of 5E17-CAR-T cells demonstrated antitumor effects in an orthotopic xenograft murine model with patient-derived GBM cells. Conclusions: Cell surface PTGFRN is a candidate target for intracranial CAR-T cell therapy for GBM. On-target off-tumor toxicity in alternative normal tissues needs to be carefully tested.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	101004
citation_title	Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma
citation_author	Kuroda, Hideki
	Kijima, Noriyuki
	Tachi, Tetsuro
	Ikeda, Shunya
	Murakami, Koki
	Nakagawa, Tomoyoshi
	Yaga, Moto
	Nakagawa, Kanji
	Utsugi, Reina
	Hirayama, Ryuichi
	Okita, Yoshiko
	Kagawa, Naoki
	Hosen, Naoki
	Kishima, Haruhiko
citation_publisher	Springer Science and Business Media Deutschland GmbH
citation_language	English
citation_date	2025-03-06
citation_journal_title	Cancer Immunology, Immunotherapy
citation_volume	74
citation_issue	4
citation_firstpage	136
citation_doi	https://doi.org/10.1007/s00262-025-03979-4
citation_public_url	https://hdl.handle.net/11094/101004