How to Optimize Extracorporeal Photopheresis

Extracorporeal photopheresis is a well-established therapy for patients with T-cell mediated diseases. It is based on collection of autologous mononuclear cells, treatment of cell suspension with 8-methoxypsoralen and UVA light, and subsequent transfusion of treated cells to the patient. Although the mechanisms of action are not fully understood, a central effect is apoptosis of mononuclear cells. The object of this study was the optimization of the process regarding 8-methoxypsoralen/UVA treatment of the cells and thus resulting lymphocyte apoptosis. In this regard, there are some parameters known which could influence the efficacy of 8-methoxypsoralen/UVA treatment, such as hematocrit or UVA dose. Concerning process optimization, we focused on the availability of the photosensitive substance and on the influence of the cell suspension matrix on the apoptosis of lymphocytes. Absorption to plastic material of the irradiation systems as well as protein binding when using autologous plasma for cell suspension reduced availability of 8-methoxypsoralen for uptake into the cells. There was an increase in T-cell apoptosis after application of 340 ng/mL 8-methoxypsoralen instead of 200 ng/mL. Apoptosis increased further by using physiological saline for cell suspension. In summary, adapting photopheresis with NaCl instead of plasma and using a higher 8-methoxypsoralen concentration led to an increase of apoptosis induction in the T-cells. To what extent this effect of an apoptosis increase has a clinical consequence has to be clarified.