Safety assessment of fluorescently labeled anti-EGFR Nanobodies in healthy dogs

Frontiers in Pharmacology

Pharmacology

Marcus C. M. Stroet¹  Nick Devoogdt¹  Sofie Pollenus¹  Sophie Hernot¹  Jens M. Debacker²  Sonja Van den Block³  Hilde De Rooster⁴  Nayra Cristina Herreira do Valle⁵  Simone Janssen⁵ 

[1] Molecular Imaging and Therapy Research Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium;Molecular Imaging and Therapy Research Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium;Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium;Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium;Molecular Imaging and Therapy Research Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium;Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium;Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium;Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium;Molecular Imaging and Therapy Research Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium;Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;

关键词: EGFR;    nanobody;    single-domain antibody;    toxicity;    dogs;    image-guided surgery;    NIR fluorescence;   

DOI  :  10.3389/fphar.2023.1266288

 received in 2023-07-24, accepted in 2023-08-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Surgical resection is one of the main treatment options for several types of cancer, the desired outcome being complete removal of the primary tumor and its local metastases. Any malignant tissue that remains after surgery may lead to relapsing disease, negatively impacting the patient’s quality of life and overall survival. Fluorescence imaging in surgical oncology aims to facilitate full resection of solid tumors through the visualization of malignant tissue during surgery, following the administration of a fluorescent contrast agent. An important class of targeting molecules are Nanobodies® (Nbs), small antigen-binding fragments derived from camelid heavy chain only antibodies. When coupled with a fluorophore, Nbs can bind to a specific receptor and demarcate tumor margins through a fluorescence camera, improving the accuracy of surgical intervention. A widely investigated target for fluorescence-guided surgery is the epidermal growth factor receptor (EGFR), which is overexpressed in several types of tumors. Promising results with the fluorescently labeled anti-EGFR Nb 7D12-s775z in murine models motivated a project employing the compound in a pioneering study in dogs with spontaneous cancer.Methods: To determine the safety profile of the study drug, three healthy purpose-bred dogs received an intravenous injection of the tracer at 5.83, 11.66, and 19.47 mg/m2, separated by a 14-day wash-out period. Physical examination and fluorescence imaging were performed at established time points, and the animals were closely monitored between doses. Blood and urine values were analyzed pre- and 24 h post administration.Results: No adverse effects were observed, and blood and urine values stayed within the reference range. Images of the oral mucosa, acquired with a fluorescence imaging device (Fluobeam®), suggest rapid clearance, which was in accordance with previous in vivo studies.Discussion: These are the first results to indicate that 7D12-s775z is well tolerated in dogs and paves the way to conduct clinical trials in canine patients with EGFR-overexpressing spontaneous tumors.

【 授权许可】

Unknown   
Copyright © 2023 Valle, Janssen, Stroet, Pollenus, Van den Block, Devoogdt, Debacker, Hernot and De Rooster.