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Cited 22 time in webofscience Cited 25 time in scopus
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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, CEvan Leeuwen, EMMIm, SJRoopenian, DCSung, YCSurh, 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
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성영철SUNG, YOUNG CHUL
Dept of Life Sciences
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