Nanobody-targeted Photodynamic Therapy for the Treatment of Feline Oral Carcinoma: a Step Towards Translation to the Veterinary Clinic

Overview

Journal Nanophotonics

Publisher De Gruyter

Date 2022 Nov 21

PMID 36405501

Authors

Irati Beltran Hernandez

Guillaume C M Grinwis

Alessia Di Maggio

Paul M P Van Bergen en Henegouwen

Wim E Hennink

Erik Teske

Jan W Hesselink

Sebastiaan A van Nimwegen

Jan A Mol

Sabrina Oliveira

Affiliations

Soon will be listed here.

Abstract

Nanobody-targeted photodynamic therapy (NB-PDT) has been developed as a potent and tumor-selective treatment, using nanobodies (NBs) to deliver a photosensitizer (PS) specifically to cancer cells. Upon local light application, reactive oxygen species are formed and consequent cell death occurs. NB-PDT has preclinically shown evident success and we next aim to treat cats with oral squamous cell carcinoma (OSCC), which has very limited therapeutic options and is regarded as a natural model of human head and neck SCC. Immunohistochemistry of feline OSCC tissue confirmed that the epidermal growth factor receptor (EGFR) is a relevant target with expression in cancer cells and not in the surrounding stroma. Three feline OSCC cell lines were employed together with a well-characterized human cancer cell line (HeLa), all with similar EGFR expression, and a low EGFR-expressing human cell line (MCF7), mirroring the EGFR expression level in the surrounding mucosal stroma. NB was identified as a NB binding human and feline EGFR with comparable high affinity. This NB was developed into NiBh, a NB-PS conjugate with high PS payload able to effectively kill feline OSCC and HeLa cell lines, after illumination. Importantly, the specificity of NB-PDT was confirmed in co-cultures where only the feline OSCC cells were killed while surrounding MCF7 cells were unaffected. Altogether, NiBh can be used for NB-PDT to treat feline OSCC and further advance NB-PDT towards the human clinic.

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