Preferred Label : Anti-PD-1/IL-2Ra/IL-2 Fusion Protein REGN10597;
NCIt synonyms : PD-1-targeted Receptor-masked IL-2 Immunocytokine REGN10597;
NCIt definition : An antibody fusion protein composed of an antibody fragment targeting the negative
immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1;
CD279) and fused to the endogenous cytokine interleukin-2 (IL-2) and masked with an
antibody fragment directed against the IL-2 receptor subunit alpha (IL2Ra; CD25) binding-site
on IL-2, with potential immunostimulating and antineoplastic activities. Upon administration,
anti-PD-1/IL-2Ra/IL-2 fusion protein REGN10597 targets and binds to PD-1 expressed
on PD-1-expressing T-cells in the tumor microenvironment (TME), thereby specifically
bringing IL-2 to the PD-1-positive T-cells in the TME. The PD-1 binding specifically
induces a confirmational change in REGN10597 that allows its IL-2 moiety to bind to
the IL-2Ra expressed on PD-1-positive CD8 T effector cells and natural killer (NK)
cells, thereby activating IL2Ra-mediated signaling within these immune cells. The
activation of cytotoxic T-lymphocytes (CTLs) and NK cells mediate cytolytic immune
responses against tumor cells causing tumor cell destruction and inhibition of tumor
cell proliferation. By selectively activating PD-1 positive T-cells with IL-2, but
not PD-1 negative bystander or naïve T-cells, the activity of tumor specific T-cells
is specifically enhanced while IL-2-induced systemic toxicity is decreased. PD-1,
a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T-cells,
functions as an immune checkpoint that negatively regulates T-cell activation and
effector function when activated by its ligands programmed cell death-1 ligand 1 (PD-L1;
cluster of differentiation 274; CD274) or 2 (PD-L2); it plays an important role in
tumor evasion from host immunity. The receptor-masked IL-2 allows for specific activation
of IL-2 in the presence of PD-1-positive cells in the TME.;
Molecule name : REGN 10597; REGN-10597;
Origin ID : C209868;
concept_is_in_subset
- has_target
