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Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
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Near-Infrared Photoimmunotherapy Using a Small Protein Mimetic for HER2-Overexpressing Breast Cancer
Haruka Yamaguchi1,2,3, Namfon Pantarat1, Takamasa Suzuki4
1Discipline of Surgery, Breast Cancer Research Unit, Basil Hetzel Institute, University of Adelaide, Adelaide, SA, 5011, Australia.
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.
Insights
Near-infrared photoimmunotherapy (NIR-PIT) using Affibody molecules shows promise for HER2-overexpressing cancers. This targeted therapy selectively destroys cancer cells, with potential for treating brain metastases.
Area of Science:
- Oncology
- Biotechnology
- Photomedicine
Background:
- Near-infrared photoimmunotherapy (NIR-PIT) utilizes antibody-photosensitizer conjugates activated by light for cancer treatment.
- Monoclonal antibodies are typically used, but their large size can limit tumor penetration and clearance.
- HER2-overexpressing cancers, including breast cancer and brain metastases, represent a significant therapeutic challenge.
Purpose of the Study:
- To investigate the efficacy of NIR-PIT using Affibody molecules, small protein mimetics, as an alternative to monoclonal antibodies for HER2-overexpressing cancers.
- To evaluate the potential of Affibody-based NIR-PIT to target cancers that express HER2, including those that have metastasized to the brain.
- To assess the safety and clinical translatability of this novel therapeutic approach.
Main Methods:
- Conjugation of HER2-specific Affibody molecules with the photosensitizer IR700Dye.
- In vitro assessment of NIR-PIT efficacy on HER2-overexpressing breast cancer cells and control cells with low HER2 expression.
- Evaluation of cell viability and cell death mechanisms following NIR light irradiation of Affibody-IR700Dye conjugates.
Main Results:
- NIR-PIT with HER2 Affibody-IR700Dye conjugates selectively induced necrotic cell death in HER2-overexpressing cancer cells.
- Cancer cell viability remained low for up to 5 days post-treatment.
- Neither high concentrations of the Affibody-dye conjugate alone nor high-dose NIR light alone affected cell viability, indicating targeted efficacy.
- Affibody molecules' small size facilitates potential blood-brain barrier penetration, suggesting utility for brain metastases.
Conclusions:
- Affibody-based NIR-PIT is a potent and selective therapeutic strategy for HER2-overexpressing cancers.
- The small size of Affibodies offers advantages in tumor penetration and potential for treating brain metastases.
- The use of clinically approved components (Affibody and IR700Dye) suggests a rapid path to clinical trials.
