Extracorporeal photopheresis is a generally accepted treatment modality for cutaneous T-cell lymphoma (CTCL) (FDA-approved), graft versus host disease (GvHD) and transplant rejection, and shows promise in various autoimmune diseases, including Crohn’s disease. The mechanism of action of ECP is not fully understood, but is thought to involve modulation of the immune system by apoptotic T cell-loaded DCs to induce immunological tolerance . ECP is currently administered using 8-methylpsoralen (8-MOP) together with the Therakos Photopheresis Systems (UVAR XTS, CELLEX). The current implementation is safe and shows clinical efficacy but there is substantial room for improvement with respect to both response rate and duration of response.
Scientists at Oslo University Hospital and Norwegian University of Science and Technology have developed an improved method for ECP, using a porphyrin precursor such as 5’-aminolevulinic acid (5-ALA) instead of the currently used 8-MOP. Ex vivo experiments in leukocytes from ECP patients have demonstrated no dark toxicity and superior leukocyte killing activity of ALA compared to 8-MOP. ALA is an approved drug with a good safety profile, when applied both systematically and topically, and has the following potential advantages:
Higher selectivity & potency. Protoporphyrin IX (PpIX) is generated from its precursor ALA and accumulated at higher level in activated T-cells and hyperproliferative cells (biologically relevant cells) Higher immunogenic potential . Targeting of cell membrane by ALA-ECP results in release and presentation of antigens with greater immunogenic potential Compatibility with visible light . ALA-derived PpIX has a primary absorption peak in the visible range (405 nm), supporting activation by visible light, while MOP requires UV-activation.
A phase I/II clinical trial of ALA-ECP is planned to be initiated in 2016Q4, enrolling CTCL and GvHD patients (5+15). The trial will evaluate safety and provide preliminary indication of efficacy.
The technology is protected by a published patent application (WO 2015/162279).