Endoscopic near infrared photoimmunotherapy using a fiber optic diffuser for peritoneal dissemination of gastric cancer. Issue 6 (29th May 2018)

• Record Type: Journal Article
• Authors: Nagaya, Tadanobu; Okuyama, Shuhei; Ogata, Fusa; Maruoka, Yasuhiro; Choyke, Peter L.; Kobayashi, Hisataka
• Is Part Of: Cancer science. Volume 109:Issue 6(2018)
• Page Start: 1902
• Page End: 1908
• Publication Date: 2018-05-29
• Subjects: endoscope -- fiber optic diffuser -- gastric cancer -- monoclonal antibodies -- near infrared photoimmunotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13621
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Near infrared photoimmunotherapy (NIR‐PIT) is a highly selective tumor treatment that employs an antibody‐photo‐absorber conjugate (APC) which is activated by near infrared light. Here, we describe the efficacy of endoscopic NIR‐PIT using the APC trastuzumab‐IR700DX (tra‐IR700) in the setting of human epidermal growth factor 2 positive (HER2 + ) gastric carcinoma with peritoneal disseminations. In this in vivo study, fluorescence endoscopy showed high tumor accumulation of tra‐IR700 within disseminated peritoneal implants. Mice with disseminated peritoneal gastric cancer were separated into 4 groups: (i) control (no treatment); (ii) tra‐IR700 i.v. only; (iii) NIR light only; and (iv) endoscopic NIR‐PIT. NIR light irradiation was carried out through a fiber optic diffuser under endoscopic guidance. In vivo bioluminescence images showed significantly greater therapeutic effect in the endoscopic NIR‐PIT group than that in the control groups ( P < .01 vs other control groups). Histological analysis showed diffuse cancer cell death in NIR‐PIT‐treated tumors. In conclusion, NIR‐PIT with NIR light delivered via an endoscopic fiber optic diffuser is a promising method for the treatment of peritoneal dissemination of gastric cancer. Moreover, this technique could be readily used in other types of cancers with peritoneal dissemination provided that suitable antibodies could be found. Abstract : Near infrared photoimmunotherapy (NIR‐PIT) is a newly‐developed cancer cell‐selective treatment that employs a targeted monoclonal antibody conjugated to a photon absorber, IRDye700DX (IR700, silica‐phthalocyanine dye). The first‐in‐human phase 1 trial of NIR‐PIT in patients with inoperable head and neck cancer targeting epidermal growth factor receptor was approved by the US FDA in 2015, and has now finished phase 2 in November 2017, then advanced to fast‐track phase 3 from January 2018. NIR‐PIT effectively induces nearly immediate necrotic/immunogenic cell death only to antibody‐photoabsorber conjugate bound target cells without damaging normal cells. This is the first study that we demonstrated NIR‐PIT successfully treated HER2‐expressing gastric cancer peritoneal dissemination using an anti‐HER2 antibody‐IR700 conjugate with intraperitoneal NIR light exposure employing a laser system equipped with an optical fiber diffuser through an endoscope system in a pre‐clinical tumor model in mice.