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Photodynamic Therapy in Immune (Non-Oncological) DisordersFocus on Benzoporphyrin Derivatives

 

作者: Leslie G. Ratkay,   J. Douglas Waterfield,   David W.C. Hunt,  

 

期刊: BioDrugs  (ADIS Available online 2000)
卷期: Volume 14, issue 2  

页码: 127-135

 

ISSN:1173-8804

 

年代: 2000

 

出版商: ADIS

 

关键词: Arthritis;Immunological disorders, treatment;Immunomodulators, therapeutic use;Photochemotherapy;Photosensitisers, therapeutic use;Psoriasis, treatment;Psoriatic arthritis, treatment;Research and development;Rheumatoid arthritis, treatment;Verteporfin, th

 

数据来源: ADIS

 

摘要:

This review examines the efficacy of photodynamic therapy in the treatment of immunological disorders. Photodynamic therapy (PDT) is a 2-step procedure. Firstly, a photosensitiser is introduced into the body, where it accumulates selectively in cells with elevated metabolism, such as cancer cells or activated cells of the immune system. Second, light is applied at a wavelength that excites the photosensitiser, producing a variety of short-lived oxygen-derived species. The effect is dependent on the doses of both photosensitiser and activating light. The mechanisms of action of PDT are multifactorial. Induction of high levels of oxidative stress results in necrotic cell death, while lower intensity oxidative stress initiates apoptosis. Sublethal doses may result in the modification of cell surface receptor expression levels and cytokine release and consequently influence cell behaviour. Immunomodulatory PDT (IPDT) utilises mainly apoptotic and sublethal doses.The studies reported here utilise verteporfin, a benzoporphyrin-derived chlorin-like photosensitiser. Veteporfin is a second generation photosensitiser, displaying rapid clearance and consequently a reduced period of skin photosensitivity compared with the first generation photosensitiser, porfimer sodium.In vivostudies showed that IPDT was effective in alleviating immunopathology in murine models of arthritis, contact hypersensitivity, experimental allergic encephalomyelitis and retention of allogeneic skin grafts. Based on these findings, early stage clinical trials with IPDT were initiated recently for the treatment of psoriasis, psoriatic arthritis and rheumatoid arthritis.While verteporfin has been the photosensitiser which pioneered IPDT, a new benzoporphyrin derivative photosensitiser, QLT0074, is under development. This has demonstrated an enhanced avidity for target cells as well as improved clearance characteristics.

 

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