Near infrared photoimmunotherapy for lung metastases

Cancer Lett. 2015 Aug 28;365(1):112-21. doi: 10.1016/j.canlet.2015.05.018. Epub 2015 May 27.

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.

Keywords: Bioluminescence; HER2 receptor; Lung metastases; Near infrared photoimmunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • BALB 3T3 Cells
  • Dose-Response Relationship, Drug
  • Female
  • Genes, Reporter
  • Immunotherapy / methods*
  • Indoles / pharmacology*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, Nude
  • Photosensitizing Agents / pharmacology*
  • Phototherapy / methods*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology
  • Time Factors
  • Tomography, X-Ray Computed
  • Transfection
  • Trastuzumab
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Indoles
  • Luminescent Proteins
  • Photosensitizing Agents
  • Receptor, ErbB-2
  • Trastuzumab
  • phthalocyanine