Suppression of Rheumatoid Arthritis by Enhanced Lymph Node Trafficking of Engineered Interleukin-10 in Murine Models.
Animals
Antigen-Presenting Cells
/ metabolism
Arthritis, Experimental
/ immunology
Arthritis, Rheumatoid
/ immunology
Disease Models, Animal
Foot
Foot Joints
/ drug effects
Hindlimb
Histocompatibility Antigens Class I
/ metabolism
Injections, Intravenous
Interleukin-10
/ pharmacology
Interleukin-17
/ immunology
Interleukin-6
/ immunology
Lymph Nodes
/ immunology
Macrophage Activation
/ drug effects
Macrophages
/ drug effects
Mice
Protein Engineering
Protein Transport
Receptors, Fc
/ metabolism
Recombinant Fusion Proteins
/ pharmacology
Serum Albumin
/ pharmacology
Transforming Growth Factor beta
/ drug effects
Tumor Necrosis Factor Inhibitors
/ pharmacology
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
13
10
2020
received:
07
04
2020
accepted:
05
11
2020
pubmed:
11
11
2020
medline:
29
5
2021
entrez:
10
11
2020
Statut:
ppublish
Résumé
Rheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials have been performed using interleukin-10 (IL-10), an antiinflammatory cytokine, as a potential treatment of RA, the therapeutic effects of IL-10 have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. This study was undertaken to engineer an IL-10-serum albumin (SA) fusion protein and evaluate its effects in 2 murine models of RA. SA-fused IL-10 (SA-IL-10) was recombinantly expressed. Mice with collagen antibody-induced arthritis (n = 4-7 per group) or collagen-induced arthritis (n = 9-15 per group) were injected intravenously with wild-type IL-10 or SA-IL-10, and the retention of SA-IL-10 in the lymph nodes (LNs), immune cell composition in the paws, and therapeutic effect of SA-IL-10 on mice with arthritis were assessed. SA fusion to IL-10 led to enhanced accumulation in the mouse LNs compared with unmodified IL-10. Intravenous SA-IL-10 treatment restored immune cell composition in the paws to a normal status, elevated the frequency of suppressive alternatively activated macrophages, reduced IL-17A levels in the paw-draining LN, and protected joint morphology. Intravenous SA-IL-10 treatment showed similar efficacy as treatment with an anti-tumor necrosis factor antibody. SA-IL-10 was equally effective when administered intravenously, locally, or subcutaneously, which is a benefit for clinical translation of this molecule. SA fusion to IL-10 is a simple but effective engineering strategy for RA therapy and has potential for clinical translation.
Substances chimiques
Histocompatibility Antigens Class I
0
Il17a protein, mouse
0
Interleukin-17
0
Interleukin-6
0
Receptors, Fc
0
Recombinant Fusion Proteins
0
Serum Albumin
0
Transforming Growth Factor beta
0
Tumor Necrosis Factor Inhibitors
0
Interleukin-10
130068-27-8
Fc receptor, neonatal
TW3XAW0RCY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
769-778Subventions
Organisme : NCI NIH HHS
ID : R01 CA219304
Pays : United States
Informations de copyright
© 2020, American College of Rheumatology.
Références
Firestein GS. Evolving concepts of rheumatoid arthritis [review]. Nature 2003;423:356-61.
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365:2205-19.
Guon Q, Wang Y, Xu D, Johannes N, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies [review]. Bone Res 2018;6:15.
Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003;48:35-45.
Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol 2008;180:5771-7.
Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy: review of a new approach. Pharmacol Rev 2003;55:241-69.
Ouyang W, O’Garra A. IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity 2019;50:871-91.
Saxena A, Khosraviani S, Noel S, Mohan D, Donner T, Hamad AR. Interleukin-10 paradox: a potent immunoregulatory cytokine that has been difficult to harness for immunotherapy. Cytokine 2015;74:27-34.
Alvarez HM, So OY, Hsieh S, Shinsky-Bjorde N, Ma H, Song Y, et al. Effects of PEGylation and immune complex formation on the pharmacokinetics and biodistribution of recombinant interleukin 10 in mice. Drug Metab Dispos 2012;40:360-73.
Schwager K, Kaspar M, Bootz F, Marcolongo R, Paresce E, Neri D, et al. Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis. Arthritis Res Ther 2009;11:R142.
Doll F, Schwager K, Hemmerle T, Neri D. Murine analogues of etanercept and of F8-IL10 inhibit the progression of collagen-induced arthritis in the mouse. Arthritis Res Ther 2013;15:R138.
Bruijnen ST, Chandrupatla DM, Giovanonni L, Neri D, Vugts DJ, Huisman MC, et al. F8-IL10: a new potential antirheumatic drug evaluated by a PET-guided translational approach. Mol Pharm 2019;16:273-81.
Ruffell B, Strachan DC, Chan V, Rosenbusch A, Ho CM, Pryer N, et al. Macrophage IL10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 2014;26:623-37.
Huber S, Gagliani N, Esplugues E, O’Connor W Jr, Huber FJ, Shaudhry A, et al. Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner. Immunity 2011;34:554-65.
Mittal SK, Cho KJ, Ishido S, Roche PA. Interleukin 10 (IL-10)-mediated immunosuppression: MARCH-I induction regulates antigen presentation by macrophages but not dendritic cells. J Biol Chem 2015;290:27158-67.
Khachigian LM, Collagen antibody-induced arthritis. Nat Protoc 2006;1:251216.
Miyasaka M, Tanaka T. Lymphocyte trafficking across high endothelial venules: dogmas and enigmas [review]. Nat Rev Immunol 2004;4:360-70.
Pyzik M, Rath T, Kuo TT, Win S, Baker K, Hubbard JJ, et al. Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury. Proc Natl Acad Sci U S A 2017;114:E2862-71.
Pyzik M, Sand KM, Hubbard JJ, Andersen JT, Sandlie I, Blumbert RS. The neonatal Fc receptor (FcRn): a misnomer? [review]. Front Immunol 2019;10:1540.
Kotake S, Yago T, Kobashigawa T, Nanke Y. The plasticity of Th17 cells in the pathogenesis of rheumatoid arthritis. J Clin Med 2017;6:E67.
Van Hamburg JP, Tas SW. Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis. J Autoimmun 2018;87:69-81.
Chiang YC, Kuo LN, Yen YH, Tang CH, Chen HY. Infection risk in patients with rheumatoid arthritis treated with etanercept or adalimumab. Comput Methods Programs Biomed 2014;116:319-27.
Downey C. Serious infection during etanercept, infliximab and adalimumab therapy for rheumatoid arthritis: a literature review. Int J Rheum Dis 2016;19:536-50.
Reid JD, Bressler B, English J. A case of adalimumab-induced pneumonitis in a 45-year-old man with Crohn’s disease. Can Respir J 2011;18:262-4.
Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, et al. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 2010;28:157-9.
Cludts I, Spinelli FR, Morello F, Hockley J, Valesini G, Wadhwa M. Anti-therapeutic antibodies and their clinical impact in patients treated with the TNF antagonist adalimumab. Cytokine 2017;96:16-23.
Wang X, Wong K, Ouyang W, Rutz S. Targeting IL-10 family cytokines for the treatment of human diseases. Cold Spring Harb Perspect Biol 2019;11:a028548.
Liu H, Moynihan KD, Zhen Y, Szeto GL, Li AV, Huang B, et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 2017;507:519-22.
Wang P, Zhao P, Dong S, Xu T, He X, Chen M, et al. An albumin-binding polypeptide both targets cytotoxic T lymphocyte vaccines to lymph nodes and boosts vaccine presentation by dendritic cells. Theranostics 2018;8:223-36.
Zhu G, Lynn GM, Jacobson O, Chen K, Liu Y, Zhang H, et al. Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy. Nat Commun 2017;8:1954.
Vandoorne K, Addadi Y, Neeman M. Visualizing vascular permeability and lymphatic drainage using labeled serum albumin. Angiogenesis 2010;13:75-85.
Yao Z, Dai W, Perry J, Brechbiel MW, Sung C. Effect of albumin fusion on the biodistribution of interleukin-2. Cancer Immunol Immunother 2004;53:404-10.
Li J, Hsu HC, Mountz JD. The dynamic duo-inflammatory M1 macrophages and Th17 cells in rheumatic diseases. J Orthop Rheumatol 2013;1:4.
Guo B. IL-10 modulates Th17 pathogenicity during autoimmune diseases. J Clin Cell Immunol 2016;7:400.
Degboé Y, Rauwel B, Baron M, Boyer JF, Ruyssen-Witrand A, Constantin A, et al. Polarization of rheumatoid macrophages by TNF targeting through an IL-10/STAT3 mechanism. Front Immunol 2019;10:3.
Avci AB, Feist E, Burmester GR. Tagering GM-CSF in rheumatoid arthritis. Clin Exp Rheumatol 2016;34:S39-44.
Schwager S, Detmar M. Inflammation and lymphatic function [review]. Front Immunol 2019;10:308.