4.7 Article

Near infrared photoimmunotherapy for lung metastases

Journal

CANCER LETTERS
Volume 365, Issue 1, Pages 112-121

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.05.018

Keywords

Near infrared photoimmunotherapy; Bioluminescence; HER2 receptor; Lung metastases

Categories

Funding

  1. National Institutes of Health, National Cancer Institute, Center for Cancer Research [ZIA BC011513-1/Intramural NIH HHS/US]

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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. Published by Elsevier Ireland Ltd.

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