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Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
Near infrared photoimmunotherapy for lung metastases
Kazuhide Sato1, Tadanobu Nagaya1, Makoto Mitsunaga1
1Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Abstract:
Lung metastases are a leading cause of cancer related deaths; nonetheless current treatments are limited. Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies that target tumors with the toxicity induced by photosensitizers activated by NIR-light. Herein, we demonstrate the efficacy of NIR-PIT in a mouse model of lung metastases. Experiments were conducted with a HER2, luciferase and GFP expressing cell line (3T3/HER2-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye700DX, was synthesized. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. With 3D culture, repeated NIR-PIT could eradicate entire spheroids. In vivo anti-tumor effects of NIR-PIT included significant reductions in both tumor volume (p = 0.0141 vs. APC) and bioluminescence image (BLI) (p = 0.0086 vs. APC) in the flank model, and prolonged survival (p < 0.0001). BLI demonstrated a significant reduction in lung metastases volume (p = 0.0117 vs. APC). Multiple NIR-PIT doses significantly prolonged survival in the lung metastasis model (p < 0.0001). These results suggested that NIR-PIT is a potential new therapy for the local control of lung metastases.
Insights
Near infrared photoimmunotherapy (NIR-PIT) effectively treats lung metastases in mice. This novel cancer therapy uses targeted antibodies and light to destroy tumors, significantly improving survival rates and reducing metastasis size.
Area of Science:
- Oncology
- Immunotherapy
- Photodynamic Therapy
Background:
- Lung metastases are a major cause of cancer mortality with limited treatment options.
- Near infrared photoimmunotherapy (NIR-PIT) offers a targeted approach combining antibody-drug conjugates and light activation for cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of NIR-PIT in a preclinical mouse model of lung metastases.
- To assess the anti-tumor effects and survival benefits of NIR-PIT for lung metastasis control.
Main Methods:
- Synthesis of an antibody-photosensitizer conjugate (APC) using trastuzumab and IRDye700DX.
- In vitro assessment of NIR-PIT-induced cytotoxicity and spheroid eradication.
- In vivo evaluation of NIR-PIT efficacy in flank and lung metastasis mouse models using bioluminescence imaging (BLI).
Main Results:
- NIR-PIT demonstrated dose-dependent cytotoxicity in vitro and eradicated 3D spheroids.
- Significant reductions in tumor volume and BLI signals were observed in flank and lung metastasis models.
- NIR-PIT treatment led to significantly prolonged survival in mice with lung metastases.
Conclusions:
- NIR-PIT is a promising therapeutic strategy for the local control of lung metastases.
- The study validates the potential of NIR-PIT as a novel cancer treatment modality.

