Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologics
Mucosal immunity is dominated by secretory IgA and IgM, although these are less favorable compared to IgG molecules for therapeutic development. Polymeric IgA and IgM are actively transported across the epithelial barrier via engagement of the polymeric Ig receptor (pIgR), but IgG molecules lack a l...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | mAbs |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2019.1708030 |
| _version_ | 1828379925991653376 |
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| author | Bharathikumar Vellalore Maruthachalam Adam Zwolak Xiefan Lin-Schmidt Edward Keough Ninkka Tamot Sathya Venkataramani Brian Geist Sanjaya Singh Rajkumar Ganesan |
| author_facet | Bharathikumar Vellalore Maruthachalam Adam Zwolak Xiefan Lin-Schmidt Edward Keough Ninkka Tamot Sathya Venkataramani Brian Geist Sanjaya Singh Rajkumar Ganesan |
| author_sort | Bharathikumar Vellalore Maruthachalam |
| collection | DOAJ |
| description | Mucosal immunity is dominated by secretory IgA and IgM, although these are less favorable compared to IgG molecules for therapeutic development. Polymeric IgA and IgM are actively transported across the epithelial barrier via engagement of the polymeric Ig receptor (pIgR), but IgG molecules lack a lumen-targeted active transport mechanism, resulting in poor biodistribution of IgG therapeutics in mucosal tissues. In this work, we describe the discovery and characterization of single-domain antibodies (VHH) that engage pIgR and undergo transepithelial transport across the mucosal epithelium. The anti-pIgR VHH panel displayed a broad range of biophysical characteristics, epitope diversity, IgA competition profiles and transcytosis activity in cell and human primary lung tissue models. Making use of this diverse VHH panel, we studied the relationship between biophysical and functional properties of anti-pIgR binders targeting different domains and epitopes of pIgR. These VHH molecules will serve as excellent tools for studying pIgR-mediated transport of biologics and for delivering multispecific IgG antibodies into mucosal lumen, where they can target and neutralize mucosal antigens. |
| first_indexed | 2024-12-10T03:49:30Z |
| format | Article |
| id | doaj.art-cc4b8f1cd804465a927601f8505a713a |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2024-12-10T03:49:30Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-cc4b8f1cd804465a927601f8505a713a2022-12-22T02:03:19ZengTaylor & Francis GroupmAbs1942-08621942-08702020-01-0112110.1080/19420862.2019.1708030Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologicsBharathikumar Vellalore Maruthachalam0Adam Zwolak1Xiefan Lin-Schmidt2Edward Keough3Ninkka Tamot4Sathya Venkataramani5Brian Geist6Sanjaya Singh7Rajkumar Ganesan8Janssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAJanssen BioTherapeutics, Janssen Research and Development, Spring House, PA, USAMucosal immunity is dominated by secretory IgA and IgM, although these are less favorable compared to IgG molecules for therapeutic development. Polymeric IgA and IgM are actively transported across the epithelial barrier via engagement of the polymeric Ig receptor (pIgR), but IgG molecules lack a lumen-targeted active transport mechanism, resulting in poor biodistribution of IgG therapeutics in mucosal tissues. In this work, we describe the discovery and characterization of single-domain antibodies (VHH) that engage pIgR and undergo transepithelial transport across the mucosal epithelium. The anti-pIgR VHH panel displayed a broad range of biophysical characteristics, epitope diversity, IgA competition profiles and transcytosis activity in cell and human primary lung tissue models. Making use of this diverse VHH panel, we studied the relationship between biophysical and functional properties of anti-pIgR binders targeting different domains and epitopes of pIgR. These VHH molecules will serve as excellent tools for studying pIgR-mediated transport of biologics and for delivering multispecific IgG antibodies into mucosal lumen, where they can target and neutralize mucosal antigens.https://www.tandfonline.com/doi/10.1080/19420862.2019.1708030Targeted deliverybiodistributionpolymeric immunoglobulin receptordimeric IgAsingle domain antibody |
| spellingShingle | Bharathikumar Vellalore Maruthachalam Adam Zwolak Xiefan Lin-Schmidt Edward Keough Ninkka Tamot Sathya Venkataramani Brian Geist Sanjaya Singh Rajkumar Ganesan Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologics mAbs Targeted delivery biodistribution polymeric immunoglobulin receptor dimeric IgA single domain antibody |
| title | Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologics |
| title_full | Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologics |
| title_fullStr | Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologics |
| title_full_unstemmed | Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologics |
| title_short | Discovery and characterization of single-domain antibodies for polymeric Ig receptor-mediated mucosal delivery of biologics |
| title_sort | discovery and characterization of single domain antibodies for polymeric ig receptor mediated mucosal delivery of biologics |
| topic | Targeted delivery biodistribution polymeric immunoglobulin receptor dimeric IgA single domain antibody |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2019.1708030 |
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