Protein chimera of IL-2-S4B6 mAb exerts similar or even higher biological activity as IL-2/S4B6 mAb immunocomplexes in vivo
-
1
Institute of Microbiology of the Academy of Sciences of the Czech Republic, Czechia
In vivo biological activity of IL-2 can be dramatically increased by complexing IL-2 with certain anti-IL-2 mAbs. The immunocomplexes of IL-2 and anti-IL-2 S4B6 mAb (henceforth IL-2/S4B6) are highly stimulatory for recently activated naïve CD8+ T cells, memory CD8+ T and NK cells (CD122high populations), and moderately stimulatory for Treg cells. Moreover, they were reported to have potent anti-tumor effects.
We designed and produced protein chimera consisting of IL-2 linked to light chain of anti-IL-2 mAb S4B6 through flexible oligopeptide spacer (Gly4Ser)3 and characterized it in terms of structure that proved to be similar to IL-2/S4B6 immunocomplexes. Moreover, in vitro and in vivo experiments showed that the protein chimera mimics IL-2/S4B6 immunocomplexes not only structurally, but also functionally as it was able to stimulate proliferation of purified and activated OT-I CD8+ T cells in vitro and induce vigorous expansion of purified CFSE-labeled OT-I CD8+ T cells activated by injection of low dose of SIINFEKL peptide in vivo. This in vivo expansion was even higher than that seen after administration of IL-2/S4B6 immunocomplexes.
In conclusion, IL-2-S4B6 mAb protein chimera mimics IL-2/S4B6 immunocomplexes structurally as well as functionally, and it is probably even more potent than its immunocomplex counterpart.
Acknowledgements
This work was supported by Czech Science Foundation grant P301/11/0325, by the Ministry of Education, Youth and Sports grant CZ.1.07/2.3.00/20.0055 and by Institutional Research Concept RVO 61388971.
Keywords:
IL-2,
protein chimera,
S4B6,
anti-IL-2 mAb,
Expression
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Tomala
J,
Kovarova
J,
Kabesova
M,
Votavova
P,
Chmelova
H,
Dvorakova
B,
Rihova
B and
Kovar
M
(2013). Protein chimera of IL-2-S4B6 mAb exerts similar or even higher biological activity as IL-2/S4B6 mAb immunocomplexes in vivo.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00047
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
08 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Jakub Tomala, Institute of Microbiology of the Academy of Sciences of the Czech Republic, Prague, Czechia, tomala@biomed.cas.cz