Anti-IL-2 [NARA1]

Absolute Antibody

Anti-IL-2 [NARA1]

7

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-

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).

Flow Cytometry, Other Application

Crystallography; in vivo; in vitro; SPR; FC

Research Use Only

Monoclonal

NARA1

IL2

interleukin 2

aldesleukin; IL-2; interleukin-2; involved in regulation of T-cell clonal expansion; lymphokine; T cell growth factor; TCGF

Mouse

IgG2a

Interleukin-2

Human

Human

The original antibody was generated immunizing Balb/c mice with human IL-2.

-20°C,2°C to 8°C

12352203