@article{eb9a95833b544ecc8fffd7d34f7cf046,
title = "Selective Depletion of Antigen-Specific Antibodies for the Treatment of Demyelinating Disease",
abstract = "Current treatments for antibody-mediated autoimmunity are associated with lack of specificity, leading to immunosuppressive effects. To overcome this limitation, we have developed a class of antibody-based therapeutics for the treatment of autoimmunity involving antibodies that recognize the autoantigen, myelin oligodendrocyte glycoprotein (MOG). These agents (“Seldegs,” for selective degradation) selectively eliminate antigen (MOG)-specific antibodies without affecting the levels of antibodies of other specificities. Seldeg treatment of mice during antibody-mediated exacerbation of experimental autoimmune encephalomyelitis by patient-derived MOG-specific antibodies results in disease amelioration. Consistent with their therapeutic effects, Seldegs deliver their targeted antibodies to Kupffer and liver sinusoidal endothelial cells that are known to have tolerogenic effects. Our results show that Seldegs can ameliorate disease mediated by MOG-specific antibodies and indicate that this approach also has the potential to treat other autoimmune diseases where the specific clearance of antibodies is required. In this study, Sun and colleagues describe a strategy to selectively remove MOG-specific antibodies that cause autoimmunity, without affecting the levels of protective antibodies of other specificities. This approach has broad potential applications for the treatment of autoimmune diseases where the specific clearance of antibodies is desirable.",
keywords = "Fc fusion proteins, antibody engineering, autoantibody, autoimmune disease, demyelinating disease, myelin oligodendrocyte glycoprotein, therapy",
author = "Wei Sun and Priyanka Khare and Xiaoli Wang and Challa, {Dilip K.} and Greenberg, {Benjamin M.} and Ober, {Raimund J.} and Ward, {E. Sally}",
note = "Funding Information: E.S.W. and R.J.O. are co-inventors on a pending patent describing Seldegs. E.S.W. and R.J.O. may receive royalties from patents owned by the UK Medical Research Council, UT Southwestern Medical Center, and Texas A&M University. E.S.W. and R.J.O. have a financial interest in argenx, Astero Biopharma, Astero Erado, and Astero Technologies. B.M.G. has received consulting fees from Alexion, Novartis, EMD Serono, Viela Bio, Genentech/Roche, Greenwich Biosciences, Axon Advisors, Rubin Anders, ABCAM, and PRIME Education. B.M.G. has received grant funding from PCORI, NIH, NMSS, The Siegel Rare Neuroimmune Association, Clene Nanomedicine, and the Guthy Jackson Charitable Foundation for NMO. B.M.G. serves as an unpaid member of the board of the Siegel Rare Neuroimmune Association. Funding Information: We are grateful to Drs. Jeffrey Ravetch and Patrick Smith for generously providing mice that transgenically express human FcγRs. We thank Joseph Heimann for assistance with expression construct generation, Dr. Ran Li for providing advice concerning PS-targeting, and Dr. Siva Devanaboyina for technical advice concerning Seldeg analyses. This work was supported in part by the Cancer Prevention and Research Institute of Texas ( RP110051 ) and Wellcome Trust ( 206411/Z/17/Z ). Raw data for all figures are available upon request. Code used to process microscopy data ( www.wardoberlab.com/software/miatool ) is available upon request. Funding Information: We are grateful to Drs. Jeffrey Ravetch and Patrick Smith for generously providing mice that transgenically express human FcγRs. We thank Joseph Heimann for assistance with expression construct generation, Dr. Ran Li for providing advice concerning PS-targeting, and Dr. Siva Devanaboyina for technical advice concerning Seldeg analyses. This work was supported in part by the Cancer Prevention and Research Institute of Texas (RP110051) and Wellcome Trust (206411/Z/17/Z). Raw data for all figures are available upon request. Code used to process microscopy data (www.wardoberlab.com/software/miatool) is available upon request. W.S. P.K. and X.W. performed the experiments. D.K.C. provided advice for the design of the in vivo and IHC experiments. B.M.G. provided essential reagents. R.J.O. and E.S.W. conceived this study and designed the experiments. W.S. P.K. B.G. R.J.O. and E.S.W. wrote the manuscript. E.S.W. and R.J.O. are co-inventors on a pending patent describing Seldegs. E.S.W. and R.J.O. may receive royalties from patents owned by the UK Medical Research Council, UT Southwestern Medical Center, and Texas A&M University. E.S.W. and R.J.O. have a financial interest in argenx, Astero Biopharma, Astero Erado, and Astero Technologies. B.M.G. has received consulting fees from Alexion, Novartis, EMD Serono, Viela Bio, Genentech/Roche, Greenwich Biosciences, Axon Advisors, Rubin Anders, ABCAM, and PRIME Education. B.M.G. has received grant funding from PCORI, NIH, NMSS, The Siegel Rare Neuroimmune Association, Clene Nanomedicine, and the Guthy Jackson Charitable Foundation for NMO. B.M.G. serves as an unpaid member of the board of the Siegel Rare Neuroimmune Association. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2021",
month = mar,
day = "3",
doi = "10.1016/j.ymthe.2020.11.017",
language = "English (US)",
volume = "29",
pages = "1312--1323",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "3",
}