Research Papers:

Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody

Tadanobu Nagaya, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Deborah W. Knapp, Sophia N. Karagiannis, Judit Fazekas-Singer, Peter L. Choyke, Amy K. LeBlanc, Erika Jensen-Jarolim and Hisataka Kobayashi _

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Oncotarget. 2018; 9:19026-19038. https://doi.org/10.18632/oncotarget.24876

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Tadanobu Nagaya1, Shuhei Okuyama1, Fusa Ogata1, Yasuhiro Maruoka1, Deborah W. Knapp2, Sophia N. Karagiannis3,4, Judit Fazekas-Singer5,6, Peter L. Choyke1, Amy K. LeBlanc7, Erika Jensen-Jarolim5,6 and Hisataka Kobayashi1

1Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

2Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA

3St. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College London, London, UK

4Breast Cancer Now Research Unit, School of Cancer and Pharmaceutical Sciences, King’s College London, Guy’s Cancer Centre, London, UK

5Comparative Medicine, The Interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria

6Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria

7Comparative Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Correspondence to:

Hisataka Kobayashi, email: [email protected]

Erika Jensen-Jarolim, email: [email protected]

Keywords: near infrared photoimmunotherapy; bladder cancer; canine cancer; EGFR; TCC

Received: January 30, 2018     Accepted: March 06, 2018     Published: April 10, 2018


Anti-epidermal growth factor receptor (EGFR) antibody therapy is used in EGFR expressing cancers including lung, colon, head and neck, and bladder cancers, however results have been modest. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate which is activated by NIR light. NIR-PIT is in clinical trials in patients with recurrent head and neck cancers using cetuximab-IR700 as the conjugate. However, its use has otherwise been restricted to mouse models. This is an effort to explore larger animal models with NIR-PIT. We describe the use of a recombinant canine anti-EGFR monoclonal antibody (mAb), can225IgG, conjugated to the photo-absorber, IR700DX, in three EGFR expressing canine transitional cell carcinoma (TCC) cell lines as a prelude to possible canine clinical studies. Can225-IR700 conjugate showed specific binding and cell-specific killing after NIR-PIT on EGFR expressing cells in vitro. In the in vivo study, can225-IR700 conjugate demonstrated accumulation of the fluorescent conjugate with high tumor-to-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 μg of can225-IR700 i.v. only; (3) NIR light exposure only; (4) 100 μg of can225-IR700 i.v., NIR light exposure. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other groups (p < 0.001), and significantly prolonged survival was achieved (p < 0.001 vs. other groups) in the treatment groups. In conclusion, NIR-PIT with can225-IR700 is a promising treatment for canine EGFR-expressing cancers, including invasive transitional cell carcinoma in pet dogs, that could provide a pathway to translation to humans.

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