Engineered clearing agents for the selective depletion of antigen-specific antibodies

Siva Charan Devanaboyina; Priyanka Khare; Dilip K Challa; Raimund J Ober; E Sally Ward

doi:10.1038/ncomms15314

Engineered clearing agents for the selective depletion of antigen-specific antibodies

Nat Commun. 2017 May 31:8:15314. doi: 10.1038/ncomms15314.

Authors

Siva Charan Devanaboyina^{1

2}, Priyanka Khare^{1

2}, Dilip K Challa^{1

2}, Raimund J Ober^{1

3}, E Sally Ward^{1

2}

Affiliations

¹ Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, 469 Joe H. Reynolds Medical Sciences Building, 1114 TAMU, College Station, Texas 77843, USA.
² Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, 3107 Medical Research &Education Building, 8447 State Highway 47, Bryan, Texas 77807, USA.
³ Department of Biomedical Engineering, Texas A&M University, 5045 Emerging Technologies Building, 3120 TAMU, College Station, Texas 77843, USA.

Abstract

Here we have designed a novel class of engineered antibody-based reagents ('Seldegs') that induce the selective degradation of antigen-specific antibodies. We demonstrate the rapid and specific clearance of antibodies recognizing the autoantigen, myelin oligodendrocyte glycoprotein and tumour target, HER2. Seldegs have considerable potential in multiple areas, including the treatment of antibody-mediated autoimmunity and diagnostic imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Neoplasm / genetics
Antigens, Neoplasm / immunology
Autoantibodies / immunology
Autoantibodies / metabolism
Autoimmune Diseases / immunology
Autoimmune Diseases / therapy*
Diagnostic Imaging / methods*
Drug Design*
Female
Histocompatibility Antigens Class I / genetics
Histocompatibility Antigens Class I / immunology*
Histocompatibility Antigens Class I / pharmacology
Histocompatibility Antigens Class I / therapeutic use
Humans
Lysosomes / immunology
Lysosomes / metabolism
Male
Mice
Mice, Inbred C57BL
Mutagenesis, Insertional
Myelin-Oligodendrocyte Glycoprotein / genetics
Myelin-Oligodendrocyte Glycoprotein / immunology
Protein Engineering / methods
Proteolysis
Receptor, ErbB-2 / genetics
Receptor, ErbB-2 / immunology
Receptors, Fc / genetics
Receptors, Fc / immunology*
Receptors, Fc / therapeutic use
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology*
Recombinant Fusion Proteins / pharmacokinetics
Recombinant Fusion Proteins / therapeutic use

Substances

Antigens, Neoplasm
Autoantibodies
Histocompatibility Antigens Class I
Myelin-Oligodendrocyte Glycoprotein
Receptors, Fc
Recombinant Fusion Proteins
ERBB2 protein, human
Receptor, ErbB-2
Fc receptor, neonatal