Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: A step towards translation to the veterinary clinic

Irati Beltrán Hernández; 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

doi:10.1515/nanoph-2021-0195

Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: A step towards translation to the veterinary clinic

Irati Beltrán Hernández, 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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. NBA 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.

Original language	English
Pages (from-to)	3075-3087
Number of pages	13
Journal	Nanophotonics
Volume	10
Issue number	12
DOIs	https://doi.org/10.1515/nanoph-2021-0195
Publication status	Published - 2 Sept 2021

Bibliographical note

Funding Information:
Research funding: This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (Grant agreement No. 677582).

Publisher Copyright:
© 2021 Irati Beltrán Hernández et al., published by De Gruyter, Berlin/Boston 2021.

Funding

Research funding: This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (Grant agreement No. 677582).

Keywords

comparative oncology
EGFR
feline cancer
nanobodies
photodynamic therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Beltrán Hernández, I., Grinwis, G. C. M., Di Maggio, A., Van Bergen En Henegouwen, P. M. P., Hennink, W. E., Teske, E., Hesselink, J. W., Van Nimwegen, S. A., Mol, J. A., & Oliveira, S. (2021). Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: A step towards translation to the veterinary clinic. Nanophotonics, 10(12), 3075-3087. https://doi.org/10.1515/nanoph-2021-0195

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title = "Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: A step towards translation to the veterinary clinic",

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. NBA 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. ",

keywords = "comparative oncology, EGFR, feline cancer, nanobodies, photodynamic therapy",

author = "\{Beltr{\'a}n Hern{\'a}ndez\}, Irati and Grinwis, \{Guillaume C.M.\} and \{Di Maggio\}, Alessia and \{Van Bergen En Henegouwen\}, \{Paul M.P.\} and Hennink, \{Wim E.\} and Erik Teske and Hesselink, \{Jan W.\} and \{Van Nimwegen\}, \{Sebastiaan A.\} and Mol, \{Jan A.\} and Sabrina Oliveira",

note = "Funding Information: Research funding: This work was supported by the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 Research and Innovation Program (Grant agreement No. 677582). Publisher Copyright: {\textcopyright} 2021 Irati Beltr{\'a}n Hern{\'a}ndez et al., published by De Gruyter, Berlin/Boston 2021.",

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month = sep,

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doi = "10.1515/nanoph-2021-0195",

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Beltrán Hernández, I , Grinwis, GCM , Di Maggio, A , Van Bergen En Henegouwen, PMP , Hennink, WE , Teske, E , Hesselink, JW , Van Nimwegen, SA, Mol, JA & Oliveira, S 2021, 'Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: A step towards translation to the veterinary clinic', Nanophotonics, vol. 10, no. 12, pp. 3075-3087. https://doi.org/10.1515/nanoph-2021-0195

TY - JOUR

T1 - Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma

T2 - A step towards translation to the veterinary clinic

AU - Beltrán Hernández, Irati

AU - Grinwis, Guillaume C.M.

AU - Di Maggio, Alessia

AU - Van Bergen En Henegouwen, Paul M.P.

AU - Hennink, Wim E.

AU - Teske, Erik

AU - Hesselink, Jan W.

AU - Van Nimwegen, Sebastiaan A.

AU - Mol, Jan A.

AU - Oliveira, Sabrina

N1 - Funding Information: Research funding: This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (Grant agreement No. 677582). Publisher Copyright: © 2021 Irati Beltrán Hernández et al., published by De Gruyter, Berlin/Boston 2021.

PY - 2021/9/2

Y1 - 2021/9/2

N2 - 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. NBA 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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Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: A step towards translation to the veterinary clinic

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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