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

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.

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective

“…The precise irradiation and evaluation of NIR light irradiation are required. For this reason, an optical fiber diffuser in the form of a flexible cylindrical optical fiber was proposed [ 112 , 113 , 114 , 115 , 116 , 117 ]. The optical fibers are utilized through the bronchoscope to deliver NIR-light to key areas.…”

Near-Infrared Photoimmunotherapy (NIR-PIT) in Urologic Cancers

“…Thus, tumors deep within the body are difficult to treat using a frontal light diffuser alone. A cylindrical light diffuser-fiber inserted into the treatment site can overcome this limitation by bringing light to the center of the tumor [ 10 , 14 , 33 , 34 ]. Using a cylindrical light diffuser, NIR light can be delivered in a cylindrical pattern (radially 1 cm from the probe for a total distance of 2 cm) to practically any tumor site via a needle, catheter, or endoscope.…”

“…Approximately one day after intravenous infusion of an IR700-based APC, NIR light is delivered to the cancer, activating a photochemical reaction that results in highly selective cancer cell killing while leaving normal tissues unaffected [ 4 , 5 , 6 , 7 ]. NIR-PIT has been used to target various cancer-specific proteins, such as epidermal growth factor receptor (EGFR) [ 8 , 9 , 10 , 11 , 12 , 13 ] and human epidermal growth factor receptor-2 (HER2) [ 14 , 15 , 16 , 17 , 18 , 19 ], and both have shown excellent anti-cancer effects. Furthermore, the clinical use of EGFR-targeted NIR-PIT progressed into clinical trials of patients with head and neck squamous cell carcinoma (HNSCC).…”

Near infrared photoimmunotherapy for cancers: A translational perspective

“…Additionally, in order to further simulate the clinical setting, orthotopic mouse models would be superior to xenografted tumour models so that the TME is more realistically recapitulated [63]. In vivo therapeutic efficacy and immune response to NIR-PIT in orthotopic mouse models of a syngeneic head and neck tumour have been demonstrated [65].…”