Psoralen Inactivation of Viruses: A Process for the Safe Manipulation of Viral Antigen and Nucleic Acid

Schneider, Katherine A.; Wronka-Edwards, Loni; Leggett-Embrey, Melissa; Walker, Eric; Sun, Peifang; Ondov, Brian D.; Wyman, Travis H; Rosovitz, M. J.; Bohn, Sherry S.; Burans, James P.; Kochel, Tadeusz J.

doi:10.3390/v7112912

Cited by 34 publications

(53 citation statements)

References 32 publications

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“…Since the method of glutaraldehyde fixation was unsuitable for maintaining Drosophila APC function while inactivating viruses in Drosophila APCs, we needed to find an alternative method. Previous studies addressing methods for inactivating RNA and DNA viruses have used psoralen treatment and UV irradiation [ 10 , 16 ]. Psoralen irreversibly binds to virus RNA or DNA when the complex between psoralen and nucleic acid is exposure to UV irradiation.…”

Section: Resultsmentioning

confidence: 99%

“…These current approaches do not, for example, preserve the native antigenicity, immunogenicity, and cell membrane integrity that is required for antigen-presenting cell function. As an alternative to these approaches, psoralen derivatives and long-wave ultraviolet light treatment can photo-react and irreversibly cross-link viral nucleic acids inside antigen-presenting cells, eliminating viral infectivity [ 10 ] while leaving surface molecules relatively unmodified. Psoralens are planar tricyclic compounds consisting of a furan ring fused to a coumarin moiety, furocoumarin [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Photochemical Treatment of Drosophila APCs Can Eliminate Associated Viruses and Maintain the APC Function for Generating Antigen-Specific CTLs Ex Vivo

Yang

Cai³

et al. 2018

Mediators of Inflammation

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Drosophila cells transfected with MHC class I and a number of costimulation molecules including B7.1, ICAM, LFA-3, and CD70 are potent antigen-presenting cells (APCs) for the generation of antigen-specific cytotoxic T cells (CTLs) in vitro. Using Drosophila APCs, CTLs specific for melanoma antigens have been generated in vitro and adoptively transferred to melanoma patients. However, the recent discovery that Drosophila cells can carry insect viruses raises the potential risk of Drosophila APCs transmitting xenogenic viruses to patient CTLs. In this study, we have investigated photoreactive methods to inactivate insect viruses in APC. A clinical grade psoralen compound, 8-MOP (UVADEX) in combination with UVA treatment (5 joules/cm2) can be used to inactivate Drosophila cell viruses. UVADEX treatment is sufficient to inactivate insect viruses but does not affect the expression of MHC class I molecules and costimulation molecules on Drosophila APCs. In fact, UVADEX treatment prevents Drosophila APC growth while maintaining APC function. Furthermore, UVADEX-treated Drosophila APCs maintain or have enhanced APC function as determined by enhanced T cell activation, proliferation, and CTL generation. Thus, the use of UVADEX-treated Drosophila APCs may provide a valuable tool for immunotherapy to generate tumor antigen-specific CTLs.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Photochemical Treatment of Drosophila APCs Can Eliminate Associated Viruses and Maintain the APC Function for Generating Antigen-Specific CTLs Ex Vivo

Yang

Cai³

et al. 2018

Mediators of Inflammation

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“…The clinical applications of the antimicrobial activity of photoactivated psoralens have largely centered on sterilization of blood products (plasma and platelet concentrates) [35]. Both viruses [36] and bacteria [37] can be efficiently killed. Amotosalen is a synthetic aminopsoralen ( Figure 3) that has been developed by Cerus Corp as the Intercept®system for pathogen inactivation [38].…”

Section: Psoralensmentioning

confidence: 99%

Oxygen-Independent Antimicrobial Photoinactivation: Type III Photochemical Mechanism?

Hamblin

Abrahamse

2020

Antibiotics

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Since the early work of the 1900s it has been axiomatic that photodynamic action requires the presence of sufficient ambient oxygen. The Type I photochemical pathway involves electron transfer reactions leading to the production of reactive oxygen species (superoxide, hydrogen peroxide, and hydroxyl radicals), while the Type II pathway involves energy transfer from the PS (photosensitizer) triplet state, leading to production of reactive singlet oxygen. The purpose of the present review is to highlight the possibility of oxygen-independent photoinactivation leading to the killing of pathogenic bacteria, which may be termed the “Type III photochemical pathway”. Psoralens can be photoactivated by ultraviolet A (UVA) light to produce DNA monoadducts and inter-strand cross-links that kill bacteria and may actually be more effective in the absence of oxygen. Tetracyclines can function as light-activated antibiotics, working by a mixture of oxygen-dependent and oxygen independent pathways. Again, covalent adducts may be formed in bacterial ribosomes. Antimicrobial photodynamic inactivation can be potentiated by addition of several different inorganic salts, and in the case of potassium iodide and sodium azide, bacterial killing can be achieved in the absence of oxygen. The proposed mechanism involves photoinduced electron transfer that produces reactive inorganic radicals. These new approaches might be useful to treat anaerobic infections or infections in hypoxic tissue.

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“…Another area that has earned much success over the past years for photodynamic inactivation of viruses is decontamination of blood products [464]. Of particular importance for blood disinfection is the use of different PSs such as riboflavin (vitamin B2) [465], methylene blue [466] , and psoralen (a derivative of amotosalen) [467]. PDT has also been successful in inactivating viruses in plants, food products, water, and environment contaminants.…”

Section: Photodynamic Treatment Of Pathogens: Antimicrobial Pdtmentioning

confidence: 99%

Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper

Silva

Saad

Thomsen

et al. 2020

J. Porphyrins Phthalocyanines

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Photodynamic therapy is a photochemistry-based approach, approved for the treatment of several malignant and non-malignant pathologies. It relies on the use of a non-toxic, light activatable chemical, photosensitizer, which preferentially accumulates in tissues/cells and, upon irradiation with the appropriate wavelength of light, confers cytotoxicity by generation of reactive molecular species. The preferential accumulation however is not universal and, depending on the anatomical site, the ratio of tumor to normal tissue may be reversed in favor of normal tissue. Under such circumstances, control of the volume of light illumination provides a second handle of selectivity. Singlet oxygen is the putative favorite reactive molecular species although other entities such as nitric oxide have been credibly implicated. Typically, most photosensitizers in current clinical use have a finite quantum yield of fluorescence which is exploited for surgery guidance and can also be incorporated for monitoring and treatment design. In addition, the photodynamic process alters the cellular, stromal, and/or vascular microenvironment transiently in a process termed photodynamic priming, making it more receptive to subsequent additional therapies including chemo- and immunotherapy. Thus, photodynamic priming may be considered as an enabling technology for the more commonly used frontline treatments. Recently, there has been an increase in the exploitation of the theranostic potential of photodynamic therapy in different preclinical and clinical settings with the use of new photosensitizer formulations and combinatorial therapeutic options. The emergence of nanomedicine has further added to the repertoire of photodynamic therapy’s potential and the convergence and co-evolution of these two exciting tools is expected to push the barriers of smart therapies, where such optical approaches might have a special niche. This review provides a perspective on current status of photodynamic therapy in anti-cancer and anti-microbial therapies and it suggests how evolving technologies combined with photochemically-initiated molecular processes may be exploited to become co-conspirators in optimization of treatment outcomes. We also project, at least for the short term, the direction that this modality may be taking in the near future.

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Psoralen Inactivation of Viruses: A Process for the Safe Manipulation of Viral Antigen and Nucleic Acid

Cited by 34 publications

References 32 publications

Photochemical Treatment of Drosophila APCs Can Eliminate Associated Viruses and Maintain the APC Function for Generating Antigen-Specific CTLs Ex Vivo

Photochemical Treatment of Drosophila APCs Can Eliminate Associated Viruses and Maintain the APC Function for Generating Antigen-Specific CTLs Ex Vivo

Oxygen-Independent Antimicrobial Photoinactivation: Type III Photochemical Mechanism?

Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper

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