United Kingdom (UK)
Recombinant monoclonal antibody to IL-2. Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the hybridoma NARA1.
UniProt Accession Number of Target Protein: P60568
Alternative Name(s) of Target: IL2; IL-2; TCGF; Interleukin-2; T-cell growth factor; Aldesleukin
Immunogen: The original antibody was generated immunizing Balb/c mice with human IL-2.
Specificity: The antibody is specific for human IL-2. The antibody binds to a three-dimensional epitope of hIL-2 (residues P34, K35, R38, T41, Q74, and K76). The antibody overlaps with the CD25-binding epitope of IL-2. The antibody does not cross reacts with mouse IL-2.
Application Notes: SPR showed the binding of the antibody to IL-2 prevented further binding of hCD25 to IL-2; the affinity of the antibody to hIL-2 was ~10−9 M. The crystal structure of the Fab fragment in complex with IL-2 was determined. IL-2/antibody complexes preferentially expand CD8+ T and NK cells in vivo while disfavoring CD25+ Tregs in transplantable metastatic melanoma model. This difference was also confirmed by kinetic proliferation studies. The complex IL-2/antibody decreased the tumor growth in mice by increasing the CD8+ T cell responses. The IL-2/antibody complex immunotherapy was also efficacious in a spontaneous melanoma model in mice. The complex Il-2/antibody shows potential as a therapeutic agent as it achieved strong antitumor immune responses (Arenas-Ramirez et al., 2016; PMID: 27903862). In order to prevent in vivo dissociation of the complex IL-2/antibody, NARA1leukin was constructed by integrating IL-2 into the antigen-binding groove on the antibody. The NARA1leukin version showed a longer half-life in vivo and more expansion of CD8+ T and NK cells, with no association with CD25, leading to a stronger antitumor response in B16-F10 murine models (Sahin et al., 2020; PMID: 33353953). The use of hIL-2/NARA1 in combination with Ezh2, an inhibitor of the histone methyltransferase enhancer of zeste homolog 2, showed enhanced tumor control in several mouse models of melanoma (Zingg et al., 2017: PMID: 28746871).
Antibody first published in:
Ramirez et al. Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2. Sci Transl Med. 2016 Nov 30;8(367):367ra166. PMID:27903862
Note on publication:
The paper describes the generation and characterization of the antibody, which is specific for IL-2 and it overlaps with the CD25-binding epitope of IL-2.