Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer (IR700Dye) that is activated by near-infrared light irradiation. We previously reported on the use of NIR-PIT with a small protein mimetic, the Affibody molecule (6...

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Autores principales:	Haruka Yamaguchi, Jotaro On, Takao Morita, Takamasa Suzuki, Yasuo Okada, Junya Ono, Andreas Evdokiou
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	photoimmunotherapy Affibody trastuzumab IR700Dye Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/81667d8a69e1484d8fb51ae8ee31edff
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spelling	oai:doaj.org-article:81667d8a69e1484d8fb51ae8ee31edff2021-11-25T17:54:25ZCombination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer10.3390/ijms2222122131422-00671661-6596https://doaj.org/article/81667d8a69e1484d8fb51ae8ee31edff2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12213https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer (IR700Dye) that is activated by near-infrared light irradiation. We previously reported on the use of NIR-PIT with a small protein mimetic, the Affibody molecule (6–7 kDa), instead of a monoclonal antibody. In this study, we investigated a combination of NIR-PIT for HER2-positive breast cancer cells (SK-BR3, MDA-MB361, and JIMT1) with HER2 Affibody-IR700Dye conjugate and trastuzumab-IR700Dye conjugate. HER2 Affibody and trastuzumab target different epitopes of the HER2 protein and do not compete. In vitro, the combination of NIR-PIT using both HER2 Affibody-IR700Dye conjugate and trastuzumab-IR700Dye conjugate induced necrotic cell death of HER2-positive breast cancer cells without damage to HER2-negative breast cancer cells (MCF7). It was more efficient than NIR-PIT using either the HER2 Affibody-IR700Dye conjugate alone or the trastuzumab-IR700Dye conjugate alone. Additionally, this combination of NIR-PIT was significantly effective against HER2 low-expressing cancer cells, trastuzumab-resistant cells (JIMT1), and brain metastatic cells of breast cancer (MDA-MB361). Furthermore, in vivo imaging exhibited the strong fluorescence intensity of both HER2 Affibody-IR700Dye conjugates and trastuzumab-Alexa488 conjugates in HER2-positive tumor, indicating that both HER2 Affibody and trastuzumab specifically bind to HER2-positive tumors without competing with each other. In conclusion, the combination of NIR-PIT using both HER2 Affibody and trastuzumab expands the targeting scope of NIR-PIT for HER2-positive breast cancer.Haruka YamaguchiJotaro OnTakao MoritaTakamasa SuzukiYasuo OkadaJunya OnoAndreas EvdokiouMDPI AGarticlephotoimmunotherapyAffibodytrastuzumabIR700DyeBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12213, p 12213 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	photoimmunotherapy Affibody trastuzumab IR700Dye Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	photoimmunotherapy Affibody trastuzumab IR700Dye Biology (General) QH301-705.5 Chemistry QD1-999 Haruka Yamaguchi Jotaro On Takao Morita Takamasa Suzuki Yasuo Okada Junya Ono Andreas Evdokiou Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer
description	Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer (IR700Dye) that is activated by near-infrared light irradiation. We previously reported on the use of NIR-PIT with a small protein mimetic, the Affibody molecule (6–7 kDa), instead of a monoclonal antibody. In this study, we investigated a combination of NIR-PIT for HER2-positive breast cancer cells (SK-BR3, MDA-MB361, and JIMT1) with HER2 Affibody-IR700Dye conjugate and trastuzumab-IR700Dye conjugate. HER2 Affibody and trastuzumab target different epitopes of the HER2 protein and do not compete. In vitro, the combination of NIR-PIT using both HER2 Affibody-IR700Dye conjugate and trastuzumab-IR700Dye conjugate induced necrotic cell death of HER2-positive breast cancer cells without damage to HER2-negative breast cancer cells (MCF7). It was more efficient than NIR-PIT using either the HER2 Affibody-IR700Dye conjugate alone or the trastuzumab-IR700Dye conjugate alone. Additionally, this combination of NIR-PIT was significantly effective against HER2 low-expressing cancer cells, trastuzumab-resistant cells (JIMT1), and brain metastatic cells of breast cancer (MDA-MB361). Furthermore, in vivo imaging exhibited the strong fluorescence intensity of both HER2 Affibody-IR700Dye conjugates and trastuzumab-Alexa488 conjugates in HER2-positive tumor, indicating that both HER2 Affibody and trastuzumab specifically bind to HER2-positive tumors without competing with each other. In conclusion, the combination of NIR-PIT using both HER2 Affibody and trastuzumab expands the targeting scope of NIR-PIT for HER2-positive breast cancer.
format	article
author	Haruka Yamaguchi Jotaro On Takao Morita Takamasa Suzuki Yasuo Okada Junya Ono Andreas Evdokiou
author_facet	Haruka Yamaguchi Jotaro On Takao Morita Takamasa Suzuki Yasuo Okada Junya Ono Andreas Evdokiou
author_sort	Haruka Yamaguchi
title	Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer
title_short	Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer
title_full	Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer
title_fullStr	Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer
title_full_unstemmed	Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer
title_sort	combination of near-infrared photoimmunotherapy using trastuzumab and small protein mimetic for her2-positive breast cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/81667d8a69e1484d8fb51ae8ee31edff
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Combination of Near-Infrared Photoimmunotherapy Using Trastuzumab and Small Protein Mimetic for HER2-Positive Breast Cancer

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