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Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally
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SYSNO ASEP 0399622 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally Author(s) Tomala, Jakub (MBU-M) RID, ORCID
Kovářová, Jiřina (MBU-M)
Kabešová, Martina (MBU-M) RID
Votavová, Petra (MBU-M) RID
Chmelová, Helena (MBU-M)
Dvořáková, Barbora (MBU-M) RID
Říhová, Blanka (MBU-M) RID
Kovář, Marek (MBU-M) RID, ORCIDSource Title ACS Chemical Biology. - : American Chemical Society - ISSN 1554-8929
Roč. 8, č. 5 (2013), s. 871-876Number of pages 6 s. Language eng - English Country US - United States Keywords IN-VIVO EXPANSION ; IL-2 ; ANTIBODY Subject RIV CE - Biochemistry R&D Projects GAP301/11/0325 GA ČR - Czech Science Foundation (CSF) Institutional support MBU-M - RVO:61388971 UT WOS 000319720700003 DOI 10.1021/cb3007242 Annotation IL-2/anti-IL-2 mAb immunocomplexes were described to have dramatically higher activity than free IL-2 in vivo. We designed protein chimera consisting of IL-2 linked to light chain of anti-IL-2 mAb S4B6 through flexible oligopeptide spacer (Gly(4)Ser)(3). This protein chimera mimics the structure of IL-2/S4B6 mAb immunocomplexes but eliminates general disadvantages of immunocomplexes like possible excess of either IL-2 or anti-IL-2 mAb and their dissociation to antibody and IL-2 at low concentrations. This novel kind of protein chimera is characterized by an intramolecular interaction between IL-2 and binding site of S4B6 mAb similarly as in IL-2/S4B6 mAb immunocomplexes. Our protein chimera has biological activity comparable to IL-2/S4B6 mAb immunocomplexes in vitro, as shown by stimulation of proliferation of purified and activated OT-I CD8(+) T cells. The protein chimera exerts higher stimulatory activity to drive expansion of purified CFSE-labeled OT-I CD8(+) T cells activated by an injection of a low dose of SIINFEKL peptide than IL-2/S4B6 mAb immunocomplexes in vivo Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2014
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