Extracorporeal photochemotherapy

Extracorporeal photochemotherapy (ECP) is a therapeutic procedure which com bines leukapheresis and PUVAtherapy (psoralen plus UVA radiation). This nov el form of cell therapy consists of collection of mononuclear cells and the ir irradiation with UVA in the presence of a photoactivable molecule (8-met hoxypsoralen), before being reinfused. ECP was developed to induce a modula tion of immune response similar to that observed after in vivo phototherapy . The photophoresis procedure requires three steps including white blood ce lls collection, and the precise control of psoralen concentration and UVA d ose. Advantages and inconvenients of the two ECP procedures available for h uman use are respectively discussed. Mechanisms of action of ECP are curren tly incompletely defined and different hypotheses are suggested. On the mol ecular level, DNA, cell membrane, and cytoplasm are involved in the biologi c effects of EPC. The therapeutic effect of ECP is likely induced by the co mbination of different biological consequences and 3 main hypotheses have b een suggested: (1) inhibition of cell proliferation and cell photodestructi on by apoptosis caused by a direct effect on DNA; (2) production of immunom odulatory cytokines induced by gene transcription; (3) immunological effect s such as EPC-induced increase of the MHC class I and II expression (which are involved in the antigen presentation), and the generation of specific s uppressor T lymphocytes CD8(+). These immunological alterations may lead to the elimination of the pathogenic T cells. Different experimental animal m odels have confirmed the in vivo modulation of immune response by ECP and h ave stimulated its use for human treatment of diseases involving benign or malignant clonal T cell proliferation (cutaneous T-cell lymphoma, autoimmun e diseases, graft - versus - host disease, allograft rejection). Although E CP appears to be a safe and well tolerated form of cell therapy, its potent ial indications remain to be further demonstrated by clinical controlled tr ials.