Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model.

Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model.:

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Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model.

Photochem Photobiol. 2020 Mar 29;:

Authors: Peng W, de Bruijn HS, Ten Hagen TLM, van Dam GM, Roodenburg JLN, Berg K, Witjes MJH, Robinson DJ

Abstract

Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti-epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study the EGFR over-expressing human head/neck OSC-19-luc2-cGFP tumour with transfected GFP gene was used in a skin-fold window-chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumour and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumour was also irradiated with 690 nm laser light 24 hours after conjugate administration. The vascular and tumour responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumour peaked at 24-48 hours after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalised in the GFP-expressing tumour cells. PDT-treated tumours showed extensive necrotic/apoptotic destruction with little vascular damage; while IHC showed no HIF-1α expression and decreased EGFR and Ki67 expression with activated caspase-3 overexpression, indicating a direct killing of tumour cells through both necrotic and apoptotic cell death.

PMID: 32222965 [PubMed - as supplied by publisher]