Near-Infrared Photoimmunotherapy Using a Small Protein Mimetic for HER2-Overexpressing Breast Cancer.

Yamaguchi Yamaguchi,Suzuki Suzuki,Evdokiou Evdokiou,Pantarat Pantarat

doi:10.3390/ijms20235835

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a new and promising cancer therapy based on a monoclonal antibody conjugated to a photosensitizer which is activated by near-infrared light irradiation, causing cell death. We investigated NIR-PIT using a small protein mimetic (6–7 kDa), Affibody molecules, instead of a monoclonal antibody for HER2-overexpressing cancer. Because of its small size, the Affibody has rapid clearance, high imaging contrast, and good tumor penetration. Due to the small size of the Affibodies, which can cross the blood–brain barrier, NIR-PIT using Affibodies has the potential to extend the target cancer of NIR-PIT, including brain metastases. In vitro, NIR-PIT using HER2 Affibody–IR700Dye conjugates induced the selective destruction of HER2-overexpressing breast cancer cells without damage to control cells having low level expression of HER2. HER2-overexpressing cancer cells showed necrotic cell death and their viability maintained at low levels, even 5 days after NIR-PIT. In contrast, treatment with high concentration of HER2 Affibody–IR700Dye conjugate alone or irradiation with high dose of NIR light alone was without effect on cell viability. Affibody and IR700Dye are currently used clinically, and therefore, we would expect the current formulation to be safely and quickly transitioned into clinical trials.

Highlights

Near-infrared photoimmunotherapy (NIR-PIT) is a new and promising cancer therapy based on the conjugate of monoclonal antibody and a photosensitizer (IR700Dye or Indocyanine green)
We aimed to evaluate the efficacy of NIR-PIT using human epidermal growth factor receptor 2 (HER2) Affibody-IR700Dye conjugate on HER2-overexpressing breast cancer cells, including cells from brain metastases
The breast cancer cell lines were first investigated for human epidermal growth factor receptor 2 (HER2) expression by immunocytochemistry (ICC) and Western blotting assay

Summary

Introduction

Near-infrared photoimmunotherapy (NIR-PIT) is a new and promising cancer therapy based on the conjugate of monoclonal antibody (mAb) and a photosensitizer (IR700Dye or Indocyanine green). Upon exposure to near-infrared light, the mAb–IR700Dye conjugate is activated, leading to necrotic cell death of cancer cells but without effect on unbound normal cells [1,2,3,4]. NIR-PIT targeting EGFR with a mAb–IR700Dye conjugate is ongoing phase II clinical evaluation for the treatment of head and neck cancer (NCT02422979). This method is applicable to other mAbs and NIR-PIT, with trastuzumab–IR700Dye targeting human epidermal growth factor receptor 2 (HER2) already reported [5,6,7,8,9]. HER2-positive cancers grow faster due to more HER2 signaling

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