Photopheresis. Therapeutic potential in preventing restenosis after percutaneous transluminal coronary angioplasty.

Photopheresis (extracorporeal photochemotherapy) is an immunomodulatory therapy that entails the reinfusion of peripheral blood mononuclear cells after exposure to the photoreactive agent methoxsalen and ultraviolet A (UVA) radiation. Currently available at approximately 150 treatment centers worldwide, photopheresis is approved by the US FDA for advanced-stage cutaneous T-cell lymphoma (CTCL) and has also shown promise in treating nonmalignant immune-related conditions such as organ transplant rejection, acute and chronic graft-versus-host disease, and autoimmune disorders. The precise mechanism by which photopheresis evokes clinical responses is unknown, although this modality seems capable of modulating T-cell and monocyte activity. Clinical and laboratory findings suggest that the reinfusion of peripheral blood mononuclear cells after exposure to UVA-activated methoxsalen engenders an immune response against proliferating T-cell clones. Methoxsalen is a naturally occurring furocoumarin that is biologically inert until exposed to UVA radiation at the proper wavelength, at which time it irreversibly cross-links DNA thymine bases and arrests cell proliferation. T cells isolated from the peripheral blood of patients after photopheresis demonstrate significantly increased levels of apoptosis, whereas macrophages and dendritic cells exhibit the ability to phagocytize the apoptotic T cells. It is surmised that photopheresis enhances the uptake, processing, and presentation of distinctive antigens from apoptotic pathogenic T cells by macrophages and dendritic cells leading to the induction of an anticlonotypic response by cytotoxic T cells. Induction by photopheresis of apparently opposite immune processes (i.e. upregulation of an antitumor response and downregulation of allogeneic or autoimmune responses) can be explained by its ability to target either a single malignant T-cell clone (as in CTCL) or multiple activated T-cell clones (as in organ transplant rejection, graft-versus-host disease, or autoimmune disease). Because acute inflammation and T-cell activation may be important in the pathogenesis of restenosis following percutaneous transluminal coronary angioplasty (PTCA), photopheresis was used for the first time at our center to prevent restenosis. A total of 78 patients with single-vessel coronary artery disease amenable to PTCA with or without stent deployment were enrolled, 41 in the control group and 37 in the photopheresis group. Clinical restenosis occurred in significantly less photopheresis patients than control patients (8 vs 27%; p = 0.04), with a relative risk of 0.30 (95% confidence interval, 0.09-1.00). A multicenter clinical trial following a US FDA-recommended protocol is currently underway to better determine what, if any, impact photopheresis has in preventing restenosis.