Modification of extracorporeal photopheresis technology with porphyrin precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in killing human T-cell lymphoma cell lines in vitro

Čunderlı́ková, Beata; Vasovič, Vlada; Randeberg, Lise Lyngsnes; Christensen, Eidi; Warloe, Trond; Nesland, Jahn M.; Peng, Qian

doi:10.1016/j.bbagen.2014.05.020

Cited by 13 publications

(12 citation statements)

References 27 publications

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“…The horizontal positioning of the photoactivation chamber makes it possible to lay whole plates in the machine, resembling the illumination of a patient's buffy coat during a standard ECP procedure. The light intensity (0.53 mW/cm 2 ) and homogeneity of the UV‐A source emitting light mainly in the region of 320–410 nm were controlled with an Ocean Optics spectrometer USB4000 (Dunedin, FL). After illumination the plates were incubated for 1 or 20 hours at 37°C before the measurement of survival of CD4 + and CD8 + T cells with flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies have established a broad biological basis for possibly improving photopheresis technology with porphyrin precursors and non‐carcinogenic visible light illumination . 5‐ALA could, for example, be advantageous in ECP because 5‐ALA‐PDT induces cell death in transformed/activated lymphocytes selectively due to an enhanced production of PpIX from 5‐ALA in these cells.…”

Section: Introductionmentioning

confidence: 99%

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Comparison between 8‐methoxypsoralen and 5‐aminolevulinic acid in killing T cells of photopheresis patients ex vivo

et al. 2018

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison between 8‐methoxypsoralen and 5‐aminolevulinic acid in killing T cells of photopheresis patients ex vivo

et al. 2018

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“…To avoid PBMC donor-related variability we used the JURKAT T-cell line, which has been previously used as a model to determine the in vitro efficacy of alternatives to 8-MOP for use in ECP [35, 36]. Advantages of this cell line include (i) cell homogeneity, which improves repeatability between experiments; (ii) composition of pathological T-cell from a lymphoma [37]; (iii) spontaneous proliferation with a constant doubling time [38]; and (iv) apoptosis kinetics similar to those of PBMCs, with a progressive increase in apoptosis 1 and 2 days after ECP treatment [35]. Two endpoints were used to assess ECP efficacy and characterize in vitro cellular kinetics after ECP treatment: inhibition of proliferation after 3 days in culture; and apoptosis after 1 and 2 days in culture.…”

Section: Introductionmentioning

confidence: 99%

A standardized methodical approach to characterize the influence of key parameters on the in vitro efficacy of extracorporeal photopheresis

et al. 2019

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Extracorporeal photopheresis (ECP) is an autologous immunomodulatory cell therapy that consists of the ex vivo collection of mononuclear cells (MNCs), which are irradiated with UVA in the presence of the photosensitizing agent 8-methoxypsoralen (8-MOP) to induce cell apoptosis. This photoactivated cell preparation is then reinfused into the patient. While the clinical benefits of ECP are well-demonstrated, no study has yet characterized the influence of variations in the composition of the cell preparation on the efficacy of ECP in vitro . Here, we describe a standardized methodology for the in vitro assessment of ECP that uses the human lymphoma T-cell line and mimics the clinical procedure. By quantifying cell apoptosis, inhibition of cell proliferation, and 8-MOP consumption, we used this approach to characterize the specific influence of key variables on the cellular response to ECP. We found that (i) increases in hematocrit and plasma concentrations attenuated the cellular response to ECP; (ii) plasma concentration was the only variable tested that influenced 8-MOP consumption; and (iii) the loss of efficacy due to variations in the concentration of certain blood components could be counteracted by modulating the UVA dose. This methodology may enable evaluation of other leukapheresis preparation protocols and better determination of the optimal working parameters for ECP.

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“…This hinders wider implementation and improvement of the immunomodulatory effect of ECP. Nevertheless, efforts have been made to optimize the ECP procedure by evaluating the use of alternative photosensitizers 17,18 or modifying other parameters, such as 8-MOP incubation time, cell density, and hematocrit. 19,20 Whether ECP can be performed in the absence of a photosensitizer with only the UVA light irradiation regime has never been evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, the usage of alternative photosensitizers can preferentially target pathogenic cells and spare desirable cells. 17,18 In addition, the influence of parameters such as hematocrit, cell density, or 8-MOP incubation time on the efficacy of ECP has been addressed in vitro. 19,20 Here, we investigated whether the standard ECP procedure, based on the combined treatment of white blood cells (WBCs) with a photosensitizer and UVA light, could be simplified by exposing the cells to UVA light only.…”

Section: Introductionmentioning

confidence: 99%

A simplified extracorporeal photopheresis procedure based on single high‐dose ultraviolet A light irradiation shows similar in vitro efficacy

Buchele

Hackstein

2020

Transfusion

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Background: Extracorporeal photopheresis (ECP) is one of the most widely used and effective cell-based therapies for the treatment of T-cell-mediated diseases. The patients' white blood cells (WBCs) are collected by apheresis and exposed to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light before retransfusion. The UVA/8-MOP combination has been in use in ECP for more than 4 decades; however, whether ECP can be simplified by UVA light irradiation only has never been analyzed. Study Design and Methods: Peripheral blood mononuclear cells were treated with classical ECP or different UVA light doses only (UVA only). Treatment efficacy was investigated by apoptosis induction in WBC subsets, inhibition of T-cell proliferation, and the ability of monocytes to induce allogeneic T-cell expansion and to respond to lipopolysaccharide and interferon-γ stimulation in vitro. Results: High-dose UVA only treatment (5 J/cm 2) was as efficient as ECP to induce apoptosis within 48 hours. UVA only treatment modulated the composition of the surviving cells by improving monocyte survival and promoting CD8 + T-cell apoptosis. Both ECP and UVA only treatment inhibited anti-CD3/ anti-CD28 triggered T-cell proliferation. Interestingly, whereas ECP-treated monocytes exhibited a markedly reduced capacity to respond to stimulation and to induce allogeneic T-cell proliferation, UVA only treatment preserved monocyte functionality to some degree. Conclusions: High-dose UVA only and standard ECP showed comparable efficacy in inducing apoptosis and inhibiting direct T-cell proliferation. Hence, UVA only treatment can be a simplified alternative to ECP therapy. Furthermore, increased monocyte survival with partially preserved functionality after UVA only treatment may provide a novel method for immunoregulation.

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Modification of extracorporeal photopheresis technology with porphyrin precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in killing human T-cell lymphoma cell lines in vitro

Cited by 13 publications

References 27 publications

Comparison between 8‐methoxypsoralen and 5‐aminolevulinic acid in killing T cells of photopheresis patients ex vivo

Comparison between 8‐methoxypsoralen and 5‐aminolevulinic acid in killing T cells of photopheresis patients ex vivo

A standardized methodical approach to characterize the influence of key parameters on the in vitro efficacy of extracorporeal photopheresis

A simplified extracorporeal photopheresis procedure based on single high‐dose ultraviolet A light irradiation shows similar in vitro efficacy

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