Generation and Analysis of Human T Cell Lines Responsive to Glatiramer Acetate (P5.363)
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Abstract
Objective: To establish a battery of human T cell lines with overall specificity for glatiramer acetate (GA), but differing in fine specificity and function, to test the immunologic bioequivalence of different preparations of GA.
Background: GA is indicated for the treatment of relapsing forms of multiple sclerosis. GA is a complex peptide composed of the amino acids YEAK, with many potential immunologic epitopes.
Design/Methods: A battery of GA-specific human T cell lines was generated from GA-naive human peripheral blood mononuclear cells via repetitive stimulation with either Copaxone® (COP) or generic Mylan GA (MGA), along with autologous antigen-presenting cells and expansion in the presence of interleukin-2. GA specificity of each T cell line was documented and the major histocompatibility complex (MHC) restriction of each line, responsiveness to altered peptide ligands, and cytokine secretory profiles were established. The reactivity of stable T cell lines was examined using multiple doses of COP and MGA to stimulate responsiveness in vitro.
Results: More than 30 GA-specific human T cell lines were generated from 3 donors. These lines exhibited different requirements for MHC Class II restricting elements, different fine specificities to di- and tri-peptides, and different responsiveness to YEAK peptides, with altered ratios of amino acids relative to GA. Additionally, individual T cell lines secreted varied cytokine profiles. Despite these differences, all T cell lines responded to multiple lots of COP and MGA comparably.
Conclusions: These results show that MGA and COP are recognized similarly by GA-specific human T cell lines, despite differences in the stimulating antigen used to generate the T cell lines, as well as the unique pattern of responsiveness of the lines. The identified GA-specific T cell lines show promise for use in a panel to compare the antigenic similarity of test and reference preparations of GA.
Disclosure: Dr. Lipsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Janssen, EMD Serono, Horizon, Sanofi, Roche, WSG&R. Dr. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee: Mylan Inc. Dr. Tjoa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment at Astarte Biologics, Inc. Dr. Lodge has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employment at Astarte Biologics, Inc. Dr. Lodge holds stock and/or stock options in I am sole owner of Astarte Biologics, and we do fund internal research. Our internal research is strictly for the development of research products and services., which sponsored research in which Dr. Lodge was involved as an investigator.
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