Endoscopic near-infrared photoimmunotherapy in an orthotopic head and neck cancer model

Cancer Sci. 2021 Aug;112(8):3041-3049. doi: 10.1111/cas.15013. Epub 2021 Jun 23.

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a cell selective cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. NIR-PIT targeting epidermal growth factor receptor (EGFR) in head and neck cancer (HNC) was conditionally approved in Japan in 2020. APC-bound tumors can be detected using endoscopic fluorescence imaging, whereas NIR light can be delivered using endoscopic fiber optics. The aims of this study were: (1) to assess the feasibility of endoscopic NIR-PIT in an orthotopic HNC model using a CD44-expressing MOC2-luc cell line; and (2) to evaluate quantitative fluorescence endoscopic imaging prior to and during NIR-PIT. The results were compared in 3 experimental groups: (1) untreated controls, (2) APC injection without light exposure (APC-IV), and (3) APC injection followed by NIR light exposure (NIR-PIT). APC injected groups showed significantly higher fluorescence signals for IR700 compared with the control group prior to therapeutic NIR light exposure, and the fluorescence signal significantly decreased in the NIR-PIT group after light exposure. After treatment, the NIR-PIT group showed significantly attenuated bioluminescence compared with the control and the APC-IV groups. Histology demonstrated diffuse necrotic death of the cancer cells in the NIR-PIT group alone. In conclusion, endoscopically delivered light combined with quantitative fluorescence imaging can be used to "see and treat" HNC. This method could also be applied to other types of cancer approachable with endoscopy.

Keywords: endoscopy; murine oral cancer; oral cancer; photoimmunotherapy.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / chemistry
  • Antineoplastic Agents, Immunological / pharmacology
  • Cell Line, Tumor
  • Endoscopy
  • Feasibility Studies
  • Female
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / therapy*
  • Hyaluronan Receptors / antagonists & inhibitors*
  • Immunotherapy
  • Indoles / administration & dosage*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Mice
  • Optical Imaging
  • Organosilicon Compounds / administration & dosage*
  • Organosilicon Compounds / chemistry
  • Organosilicon Compounds / pharmacology
  • Phototherapy
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Immunological
  • Cd44 protein, mouse
  • Hyaluronan Receptors
  • IRDye700DX N-hydroxysuccinimide ester
  • Indoles
  • Organosilicon Compounds