IL-7/anti-IL-7 mAb complexes augment cytokine potency in mice through association with IgG-Fc and by competition with IL-7R
SCIE
SCOPUS
- Title
- IL-7/anti-IL-7 mAb complexes augment cytokine potency in mice through association with IgG-Fc and by competition with IL-7R
- Authors
- Martin, CE; van Leeuwen, EMM; Im, SJ; Roopenian, DC; Sung, YC; Surh, CD
- Date Issued
- 2013-05-30
- Publisher
- AMER SOC HEMATOLOGY
- Abstract
- Interleukin-7 (IL-7) is essential to T-cell survival as well as homeostatic proliferation, and clinical trials that exploit the mitogenic effects of IL-7 have achieved success in treating human diseases. In mice, the in vivo potency of IL-7 improves dramatically when it is administered as a complex with the anti-IL-7 neutralizing monoclonal antibody clone M25. However, the mechanism whereby M25 augments IL-7 potency is unknown. We have analyzed the discrete contributions of the antibody constant (Fc) and IL-7-binding (Fab) domains to the mechanism. By engaging the neonatal Fc receptor the Fc domain extends the in vivo lifespan of IL-7/M25 complexes and accounts for the majority of their activity. Unexpectedly, the IL-7-neutralizing Fab domain provides an additional, albeit smaller, contribution, possibly by serving as a cytokine depot. This study is the first to demonstrate that the neutralizing aspect of the monoclonal antibody is directly involved in enhancing the potency of a cytokine with a single form of receptor. Lessons from the mechanism of IL-7/M25 complexes inform the design of next-generation cytokine therapeutics.
- Keywords
- T-CELL HOMEOSTASIS; IN-VIVO; RECOMBINANT INTERLEUKIN-2; SELECTIVE STIMULATION; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSES; LYMPHOID ORGANS; DEFICIENT MICE; RECEPTOR; ENHANCEMENT
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/27419
- DOI
- 10.1182/BLOOD-2012-08-449215
- ISSN
- 0006-4971
- Article Type
- Article
- Citation
- BLOOD, vol. 121, no. 22, page. 4484 - 4492, 2013-05-30
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.