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Mono- and tri-cationic porphyrin-monoclonal antibody conjugates: photodynamic activity and mechanism of action

Smith, Karen; Malatesti, Nela; Cauchon, Nicole; Hunting, Darel; Lecomte, Roger; van Lier, Johan E.; Greenman, John; Boyle, Ross W.

Authors

Karen Smith

Nela Malatesti

Nicole Cauchon

Darel Hunting

Roger Lecomte

Johan E. van Lier



Abstract

Two cationic porphyrins bearing an isothiocyanate group for conjugation to monocolonal antibodies have been synthesized. The two porphyrins conjugated efficiently to three monoclonal antibodies (anti-CD104, anti-CD146 and anti-CD326), which recognize antigens commonly over-expressed on a range of tumour cells. In vitro, all conjugates retained the phototoxicity of the porphyrin and the immunoreactivity of the antibody. Mechanistic studies showed that conjugates formed from the mono- and tri-cationic porphyrin and anti-CD104 antibody mediated apoptosis following irradiation with non-thermal red light of 630±15nm wavelength. In vivo antibody conjugates caused suppression of human LoVo tumour growth in immunodeficient NIH III mice, similar to the commercial photodynamic therapy (PDT) agent Photofrin®, but at administered photosensitizer doses that were more than two orders of magnitude lower. Positron emission tomography (PET) following PDT showed a large, early increase in uptake of 18fluorodeoxyglucose (FDG) by tumours treated with the anti-CD104 conjugates. This effect was not observed with Photofrin® or with conjugates formed from the same photosensitizers conjugated to an irrelevant antibody.

Journal Article Type Article
Publication Date 2011-02
Journal IMMUNOLOGY
Print ISSN 0019-2805
Electronic ISSN 1365-2567
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 132
Issue 2
Pages 256-265
APA6 Citation Smith, K., Malatesti, N., Cauchon, N., Hunting, D., Lecomte, R., van Lier, J. E., …Boyle, R. W. (2011). Mono- and tri-cationic porphyrin-monoclonal antibody conjugates: photodynamic activity and mechanism of action. Immunology, 132(2), 256-265. https://doi.org/10.1111/j.1365-2567.2010.03359.x
DOI https://doi.org/10.1111/j.1365-2567.2010.03359.x
Keywords Bioconjugation; Head and neck cancer; Monoclonal antibody; Photodynamic therapy
Publisher URL https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2567.2010.03359.x
Copyright Statement Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibra...neopen#OnlineOpen_Terms

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Copyright Statement
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms





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