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Depletion of activated macrophages with a folate receptor-beta-specific antibody improves symptoms in mouse models of rheumatoid arthritis

  1. Author:
    Hu, Yingwen
    Wang, Bingbing
    Shen, Jiayin
    Low, Stewart A
    Putt, Karson S
    Niessen, Hans W M
    Matteson, Eric L
    Murphy, Linda
    Ruppert, Clemens
    Jansen, Gerrit
    Oliver, Stephen J
    Feng,Yang
    Dimitrov, Dimiter S
    Nickerson-Nutter, Cheryl
    Low, Philip S

  2. Author Address

    Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA., Institute for Drug Discovery, Purdue University, West Lafayette, IN, 47907, USA., Department of Pathology and Cardiac Surgery, ACS, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands., Division of Rheumatology, and Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA., Justus-Liebig University Giessen, Department of Internal Medicine, Biomedizinisches Forschungszentrum Seltersberg, Giessen, Germany., Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands., Department of Medicine, New York University School of Medicine, New York, NY, USA., Protein Interactions Section, Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD, 21702, USA., Center for Antibody Therapeutics, University of Pittsburgh, Pittsburgh, PA, 15216, USA., HuLow Medical, Northbrook, IL, USA., Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN, 47907, USA. plow@purdue.edu., Institute for Drug Discovery, Purdue University, West Lafayette, IN, 47907, USA. plow@purdue.edu.,
    1. Year: 2019
    2. Date: Jun 07
    3. Epub Date: 2019 06 07
  2. Journal: Arthritis research & therapy
    1. 21
    2. 1
    3. Pages: 143
  4. Type of Article: Article
  5. Article Number: 143
  6. ISSN: 1478-6354
  1. Abstract:

    Objectives: Most therapies for autoimmune and inflammatory diseases either neutralize or suppress production of inflammatory cytokines produced by activated macrophages (e.g., TNF, IL-1, IL-6, IL-17, GM-CSF). However, no approved therapies directly target this activated subset of macrophages.MethodsFirst, we undertook to examine whether the folate receptor beta (FR-) positive subpopulation of macrophages, which marks the inflammatory subset in animal models of rheumatoid arthritis, might constitute the prominent population of macrophages in inflamed lesions in humans. Next, we utilized anti-FR- monoclonal antibodies capable of mediating antibody-dependent cell cytotoxicity (ADCC) to treat animal models of rheumatoid arthritis and peritonitis.Results: Human tissue samples of rheumatoid arthritis, Crohn's disease, ulcerative colitis, idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, chronic obstructive pulmonary disease, systemic lupus erythematosus, psoriasis, and scleroderma are all characterized by dramatic accumulation of macrophages that express FR-, a protein not expressed on resting macrophages or any other healthy tissues. A monoclonal antibody to FR- accumulates specifically in inflamed lesions of murine inflammatory disease models and successfully treats such models of rheumatoid arthritis and peritonitis. More importantly, elimination of FR--positive macrophages upon treatment with an anti-FR- monoclonal antibody promotes the departure of other immune cells, including T cells, B cells, neutrophils, and dendritic cells from the inflamed lesions.Conclusions: These data suggest that specific elimination of FR--expressing macrophages may constitute a highly specific therapy for multiple autoimmune and inflammatory diseases and that a recently developed human anti-human FR- monoclonal antibody (m909) might contribute to suppression of this subpopulation of macrophages.

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External Sources

  1. View Full Text
  2. DOI: 10.1186/s13075-019-1912-0
  3. PMID: 31174578
  4. View record in Web of Science®
  5. WOS: 000470697100001
  6. PII : 10.1186/s13075-019-1912-0

Library Notes

  1. Fiscal Year: FY2018-2019
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