Ann Neurol. 2004 Mar;55(3):390-9
Weiner LP, Louie KA, Atalla LR, Kochounian HH, Du J, Wei W, Hinton DR, Gordon EM, Anderson WF, McMillan M.
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Female SJL/J mice, suffering from experimental autoimmune encephalomyelitis (EAE), were injected with 1 x 10(7) cells from a syngeneic fibroblast line transduced with a retroviral vector designed to encode proteolipid protein (101-157) targeted for secretion.
A striking abrogation of both clinical and histological signs of disease resulted.
The treatment was efficacious when given after the first or the third relapses, protected naive mice from challenge with spinal cord homogenate, and was dose dependent.
This strategy was devised to provide a systemic, antigen-specific signal to pathogenic T cells in the absence of costimulation and, hence, render them anergic.
Cytokine analyses of brain and spinal cord lymphocytes demonstrate that the treatment induces an antiinflammatory Th2 profile, indicating that this antigen-specific therapy acts by a cytokine-induced pathway.
This study was designed for translation to the clinic.
We envision using allogeneic transduced fibroblasts, encapsulated in a chamber, to deliver the antigen-specific signal.
This will enable us to use one therapeutic cell line for all patients and to remove the device should the therapy exacerbate disease.