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.
Johan E. van Lier
Professor John Greenman J.Greenman@hull.ac.uk
Professor of Tumour Immunology
Professor Ross Boyle R.W.Boyle@hull.ac.uk
Professor of Biological Chemistry
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|
|Peer Reviewed||Peer Reviewed|
|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|
|Keywords||Bioconjugation; Head and neck cancer; Monoclonal antibody; Photodynamic therapy|
|Copyright Statement||Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibra...neopen#OnlineOpen_Terms|
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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