Preferred Label : IL-15 Superagonist SOT201;
NCIt synonyms : Anti-PD-1 Antibody-IL-15 Fusion Protein SOT201; IL-15/PD-1-targeting Immunocytokine SOT201;
NCIt definition : A cis-acting immunocytokine and antibody cytokine fusion protein composed of a humanized,
Fc-silenced monoclonal antibody against the human negative immunoregulatory checkpoint
receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) fused to a covalent
receptor-linker interleukin-15 (RLI-15) complex containing a human attenuated IL-15
mutein linked to the high-affinity binding sushi domain site of the IL-15 receptor
alpha (IL-15Ralpha; IL-15Ra), with potential immunomodulatory and antineoplastic activities.
Upon administration, IL-15 superagonist SOT201 targets and binds, with its anti-PD-1
moiety, to PD-1-expressing tumor-infiltrating lymphocytes (TILs), thereby blocking
PD-1-mediated T-cell signaling in these cells in the tumor microenvironment (TME).
This brings the IL-15 moiety to PD-1-expressing TILs in the TME. The attenuated IL-15
mutein moiety targets and binds, via the IL-2/IL-15betagamma receptor (IL-2/IL-15
receptor beta-common gamma chain), to antigen-specific PD-1-positive CD8 T-cells
and natural killer cells (NK cells) without stimulating regulatory T-cells (Tregs).
This activates and increases the levels of NKs and antigen-specific PD-1-positive
CD8 T-cells. The cytotoxic T-lymphocytes (CTLs) enhance the secretion of the cytokine
interferon-gamma (IFN-g), which further potentiates the immune response against tumor
cells. This may increase CTL-mediated tumor cell killing and decrease tumor cell proliferation.
IL-15 regulates CD8 T and NK cell development, activation, and proliferation. The
Fc moiety allows for an extended half-life of SOT201 while cross linking IL-15 with
IL-15Ra sushi domain improves stability. 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; B7-H1; CD274) and 2 (PD-L2); it plays an important role
in tumor evasion from host immunity.;
Molecule name : SOT-201; SOT 201;
NCI Metathesaurus CUI : CL1926560;
Origin ID : C204467;
UMLS CUI : C5908049;
Semantic type(s)
- concept_is_in_subset
