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Proceedings Paper

Photosensitizers for photodynamic immune modulation
Author(s): John R. North; Ronald Boch; David W. C. Hunt; Leslie G. Ratkay; Guillermo O. Simkin; Jing-Song Tao; Anna M. Richter; Julia G. Levy
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Paper Abstract

PDT may be an effective treatment for certain immune-mediated disorders. The immunomodulatory action of PDT is likely a consequence of effects exerted at a number of levels including stimulation of specific cell signaling pathways, selective depletion of activated immune cells, alteration of receptor expression by immune and non-immune cells, and the modulation of cytokine availability. QLT0074, a potent photosensitizer that exhibits rapid clearance kinetics in vivo, is in development for the treatment of immune disorders. In comparison to the well-characterized and structurally related photosensitizer verteporfin, lower concentrations of QLT0074 were required to induce apoptosis in human blood T cells and keratinocytes using blue light for photoactivation. Both photosensitizers triggered the stress activated protein kinase (SAPK) and p38 (HOG1) pathways but not extracellularly regulated kinase (ERK) activity in mouse Pam212 keratinocytes. In cell signaling responses, QLT0074 was active at lower concentrations than verteporfin. For all in vitro test systems, the stronger photodynamic activity of QLT0074 was associated with a greater cell uptake of this photosensitize than verteporfin. In mouse immune models, sub-erythemogenic doses of QLT0074 in combination with whole body blue light irradiation inhibited the contact hypersensitivity response and limited the development of adjuvant-induced arthritis. QLT0074 exhibits activities that indicate it may be a favorable agent for the photodynamic treatment of human immune disease.

Paper Details

Date Published: 13 June 2000
PDF: 12 pages
Proc. SPIE 3914, Laser-Tissue Interaction XI: Photochemical, Photothermal, and Photomechanical, (13 June 2000); doi: 10.1117/12.388020
Show Author Affiliations
John R. North, QLT PhotoTherapeutics, Inc. (Canada)
Ronald Boch, QLT PhotoTherapeutics, Inc. (Canada)
David W. C. Hunt, QLT PhotoTherapeutics, Inc. (Canada)
Leslie G. Ratkay, QLT PhotoTherapeutics, Inc. (Canada)
Guillermo O. Simkin, QLT PhotoTherapeutics, Inc. (Canada)
Jing-Song Tao, QLT PhotoTherapeutics, Inc. (Canada)
Anna M. Richter, QLT PhotoTherapeutics, Inc. (Canada)
Julia G. Levy, QLT PhotoTherapeutics, Inc. (Canada)

Published in SPIE Proceedings Vol. 3914:
Laser-Tissue Interaction XI: Photochemical, Photothermal, and Photomechanical
Jeffrey O. Hollinger D.D.S.; Donald Dean Duncan; Jeffrey O. Hollinger D.D.S.; Donald Dean Duncan; Steven L. Jacques, Editor(s)

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