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.

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.

Citation

Smith, K., Malatesti, N., Cauchon, N., Hunting, D., Lecomte, R., van Lier, J. E., Greenman, J., & 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

• Journal Article Type: Article
• Acceptance Date: Aug 24, 2010
• Online Publication Date: Oct 29, 2010
• Publication Date: 2011-02
• Journal: IMMUNOLOGY
• Print ISSN: 0019-2805
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 132
• Issue: 2
• Pages: 256-265
• DOI: https://doi.org/10.1111/j.1365-2567.2010.03359.x
• Keywords: Bioconjugation; Head and neck cancer; Monoclonal antibody; Photodynamic therapy
• Public URL: https://hull-repository.worktribe.com/output/400121
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2567.2010.03359.x
• Contract Date: Sep 12, 2018