A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis

Oyama, Shohei; Ebina, Kosuke; Etani, Yuki; Hirao, Makoto; Kyuuma, Masanao; Fujii, Yasuyuki; Iwata, Katsuya; Ogawa, Bunichiro; Hasegawa, Tomoya; Kawano, Sasagu; Nakanishi, Yutaka; Okada, Seiji; Nakata, Ken

doi:https://doi.org/10.1038/s41598-022-23152-6

A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis

Oyama, Shohei; Ebina, Kosuke; Etani, Yuki et al.

Scientific Reports, 2022, 12(1), 18102

Number of Access:1,404（2025-07-24 02:07 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93205

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Title	A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis
Creator	CreatorName Oyama, Shohei
	NRID 1000070612076 1000070612076 researchmap permalink k-ebina k-ebina Scopus Author ID 8415453300 8415453300 ORCID 0000-0002-2426-1024 0000-0002-2426-1024 CreatorName Ebina, Kosuke
	NRID 1000060898930 1000060898930 ORCID 0000-0001-5741-5969 0000-0001-5741-5969 researchmap permalink Yetani0302 Yetani0302 CreatorName Etani, Yuki
	NRID 1000010527708 1000010527708 Scopus Author ID 8883255100 8883255100 CreatorName Hirao, Makoto
	CreatorName Kyuuma, Masanao
	CreatorName Fujii, Yasuyuki
	CreatorName Iwata, Katsuya
	CreatorName Ogawa, Bunichiro
	CreatorName Hasegawa, Tomoya
	CreatorName Kawano, Sasagu
	CreatorName Nakanishi, Yutaka
	NRID 1000030448435 1000030448435 ORCID 0000-0002-5107-8209 0000-0002-5107-8209 researchmap permalink okadaseiji okadaseiji Scopus Author ID 35079139100 35079139100 CreatorName Okada, Seiji
	NRID 1000000283747 1000000283747 researchmap permalink ken-nakata ken-nakata Scopus Author ID 7402151308 7402151308 CreatorName Nakata, Ken
Description	Oyama S., Ebina K., Etani Y., et al. A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis. Scientific Reports 12, 18102 (2022); https://doi.org/10.1038/s41598-022-23152-6.
Abstract	In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the subcutaneous injection. To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. Alexa Fluor 680-labeled ozoralizumab and adalimumab were administered by subcutaneous injection once (2 mg/kg) at five weeks after induction of collagen-induced arthritis (CIA) in an animal arthritis model. The time-course of changes in the fluorescence intensities of the two compounds in the paws and serum were evaluated. The paws of the CIA mice were harvested at four and eight hours after the injection for fluorescence microscopy. Biofluorescence imaging revealed better distribution of ozoralizumab to the joint tissues than of adalimumab, as early as at four hours after the injection. Fluorescence microscopy revealed a greater fluorescence intensity of ozoralizumab in the joint tissues than that of adalimumab at eight hours after the injection. Ozoralizumab showed a significantly higher absorption rate constant as compared with adalimumab. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice.
Publisher	Nature Research
Source Title	Scientific Reports
Volume (Issue)	12(1)
Page	18102
Date of Issued	2022-10-27
Language	English
Handle URL	https://hdl.handle.net/11094/93205
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-022-23152-6
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
DCMI Type	Text
DCTERMS.bibliographicCitation	Scientific Reports. 2022, 12(1), p. 18102
DC.title	A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis
DC.creator	Oyama, Shohei
	Ebina, Kosuke
	Etani, Yuki
	Hirao, Makoto
	Kyuuma, Masanao
	Fujii, Yasuyuki
	Iwata, Katsuya
	Ogawa, Bunichiro
	Hasegawa, Tomoya
	Kawano, Sasagu
	Nakanishi, Yutaka
	Okada, Seiji
	Nakata, Ken
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2022-10-27
DC.identifier	https://doi.org/10.1038/s41598-022-23152-6
DC.description	Oyama S., Ebina K., Etani Y., et al. A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis. Scientific Reports 12, 18102 (2022); https://doi.org/10.1038/s41598-022-23152-6.
DCTERMS.abstract	In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the subcutaneous injection. To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. Alexa Fluor 680-labeled ozoralizumab and adalimumab were administered by subcutaneous injection once (2 mg/kg) at five weeks after induction of collagen-induced arthritis (CIA) in an animal arthritis model. The time-course of changes in the fluorescence intensities of the two compounds in the paws and serum were evaluated. The paws of the CIA mice were harvested at four and eight hours after the injection for fluorescence microscopy. Biofluorescence imaging revealed better distribution of ozoralizumab to the joint tissues than of adalimumab, as early as at four hours after the injection. Fluorescence microscopy revealed a greater fluorescence intensity of ozoralizumab in the joint tissues than that of adalimumab at eight hours after the injection. Ozoralizumab showed a significantly higher absorption rate constant as compared with adalimumab. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93205
citation_title	A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis
citation_author	Oyama, Shohei
	Ebina, Kosuke
	Etani, Yuki
	Hirao, Makoto
	Kyuuma, Masanao
	Fujii, Yasuyuki
	Iwata, Katsuya
	Ogawa, Bunichiro
	Hasegawa, Tomoya
	Kawano, Sasagu
	Nakanishi, Yutaka
	Okada, Seiji
	Nakata, Ken
citation_publisher	Nature Research
citation_language	English
citation_date	2022-10-27
citation_journal_title	Scientific Reports
citation_volume	12
citation_issue	1
citation_firstpage	18102
citation_doi	https://doi.org/10.1038/s41598-022-23152-6
citation_public_url	https://hdl.handle.net/11094/93205

A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis

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