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

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

  • Int J Mol Sci. 2021 Nov 11;22(22):12213. doi: 10.3390/ijms222212213.
Haruka Yamaguchi 1 2,  Jotaro On 3,  Takao Morita 1,  Takamasa Suzuki 4,  Yasuo Okada 5,  Junya Ono 5,  Andreas Evdokiou 2
Affiliations

Affiliations

  • 1 Department of Biochemistry, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan.
  • 2 Discipline of Surgery, Breast Cancer Research Unit, Basil Hetzel Institute, University of Adelaide, Adelaide, SA 5011, Australia.
  • 3 Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8122, Japan.
  • 4 Faculty of Engineering, Niigata University, Niigata 950-2181, Japan.
  • 5 Department of Pathology, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan.
PMID: 34830099 DOI: 10.3390/ijms222212213
Abstract

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.

Keywords

Affibody; IR700Dye; photoimmunotherapy; trastuzumab.

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