Preferred Label : PD-L1/4-1BB/HSA Trispecific Fusion Protein NM21-1480;
NCIt synonyms : PD-L1/4-1BB/HSA Trispecific scDb-scFv NM21-1480; alphaPD-L1/4-1BB/HSA NM21-1480; PD-L1/4-1BB/HSA Trispecific scMATCH3 NM21-1480; Trispecific Anti-PD-L1/anti-4-1BB/anti-Human Serum Albumin (HSA) scFv Fusion Protein
NM21-1480; alphaPD-L1/alpha4-1BB/alphaHSA NM21-1480;
NCIt related terms : NM-21-1480;
NCIt definition : A recombinant, trispecific monovalent antibody-based molecule targeting the human
programmed death-ligand 1 (PD-L1), 4-1BB (CD137; tumor necrosis factor receptor superfamily
member 9; TNFRSF9) and human serum albumin (HSA), with potential checkpoint inhibitory,
immunostimulating and antineoplastic activities. PD-L1/4-1BB/HSA trispecific fusion
protein NM21-1480 consists of three monovalent antibody Fvs specific for PD-L1, HSA
and 4-1BB fused in a single chain. Upon administration, PD-L1/4-1BB/HSA trispecific
fusion protein NM21-1480 simultaneously targets and binds to a membrane-distal epitope
of 4-1BB, which is expressed on a variety of leukocyte subsets including activated
T-lymphocytes, and PD-L1 expressed on tumor cells. The simultaneous binding to PD-L1
enables clustering of 4-1BB and thereby allows for conditional stimulation of 4-1BB
signaling in the tumor microenvironment (TME) only upon binding to PD-L1 on tumor
cells. 4-1BB activation results in T-cell stimulation and enhances T-lymphocyte-mediated
anti-tumor activity. At the same time, NM21-1480 prevents PD-L1 from binding to and
activating its receptor, programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1).
This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances
cytotoxic T-cell-mediated tumor cell lysis, which may lead to a reduction in tumor
growth. PD-L1 binding to PD-1 on activated T-cells inhibits the expansion and survival
of CD8-positive T-cells, suppresses the immune system and results in immune evasion.
4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is
an inducible costimulatory receptor that plays a key role in T-cell proliferation,
survival and cytolytic activity. HSA fusion prolongs the half-life of NM21-1480. The
conditional activation of 4-1BB signaling prevents systemic T-cell activation and
lowers toxicity.;
UNII : E6OIF2QOI3;
Molecule name : ND 021; NM21-1480; NM21 1480; ND-021;
NCI Metathesaurus CUI : CL1407921;
Origin ID : C174020;
UMLS CUI : C5418053;
Semantic type(s)
- concept_is_in_subset
- has_target
