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Generation and characterization of human anti-human IL-21 neutralizing monoclonal antibodies
| Content Provider | Scilit |
|---|---|
| Author | Maurer, Mark F. Garrigues, Ursula Jaspers, Stephen R. Meengs, Brent Rixon, Mark W. Stevens, Brenda L. Lewis, Kenneth B. Julien, Susan H. Bukowski, Thomas R. Wolf, Anitra C. Hamacher, Nels B. Snavely, Mark Dillon, Stacey R. |
| Copyright Year | 2012 |
| Description | Journal: mAbs Interleukin-21 (IL-21) is a type I four-helical bundle cytokine that exerts a variety of significant effects on many hematopoietic cells, including T and B lymphocytes and natural killer cells. IL-21 is produced predominantly by CD4+ T cells and natural killer T cells and, when aberrantly overexpressed, appears to play important roles in a wide variety of autoimmune disorders. To generate potential therapeutic reagents capable of inhibiting IL-21 for clinical use, we immunized human immunoglobulin transgenic mice with IL-21 and then identified and cloned a panel of human anti-human IL-21 binding monoclonal antibodies. IL-21 neutralizing and IL-21-binding, non-neutralizing antibodies were assigned to distinct epitope "bins" based on surface plasmon resonance competition studies. The most potent neutralizing antibodies had extremely high (sub pM) affinity for IL-21 and were able to block IL-21 activity in various biological assays using either an IL-21R-transfected pre-B-cell line or primary human B cells, and their neutralizing activity was, in some cases, superior to that of a soluble form of the high affinity heterodimeric IL-21 receptor. Characterization of this panel of IL-21 antibodies provided the basis for the selection of a therapeutic candidate antibody capable of inhibiting IL-21 activity for the treatment of autoimmune and inflammatory diseases. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/mabs.4.1.18713?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338942/pdf https://www.landesbioscience.com/journals/mabs/MaurerMABS4-1-X.pdf |
| Ending Page | 83 |
| Page Count | 15 |
| Starting Page | 69 |
| ISSN | 19420862 |
| e-ISSN | 19420870 |
| DOI | 10.4161/mabs.4.1.18713 |
| Journal | mAbs |
| Issue Number | 1 |
| Volume Number | 4 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2012-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: mAbs Biochemistry and Molecular Biology Interleukin 21 Human Ig Transgenic Mice Autoimmunity |
| Content Type | Text |
| Subject | Immunology and Allergy Immunology |
