Preferred Label : Anti-PD-1/Anti-CD73 Bispecific Antibody AK131;
NCIt synonyms : Anti-CD73/Anti-PD-1 Bispecific Antibody AK131; Anti-PD-1/CD73 Bispecific Antibody AK131; PD-1 x CD73 Bispecific Antibody AK131;
NCIt definition : A bispecific antibody derived from penpulimab and dresbuxelimab and directed against
the negative immunoregulatory human cell receptor programmed cell death protein 1
(PD-1; PDCD1; CD279) and the ectoenzyme 5'-ecto-nucleotidase (cluster of differentiation
73; CD73; 5'-NT; ecto-5'-nucleotidase; NT5E), with potential immune checkpoint inhibitory,
immunomodulating and antineoplastic activities. Upon administration, anti-PD-1/anti-CD73
bispecific antibody AK131 simultaneously targets and binds to both PD-1 expressed
on T-cells and CD73 expressed on tumor cells. The binding of AK131 to PD-1 prevents
the activation of PD-1 by its ligands, programmed cell death-1 ligand 1 (PD-L1; CD274)
and 2 (PD-L2; CD273). This abrogates T-cell inhibition, activates antigen-specific
T-lymphocytes and enhances cytotoxic T-lymphocyte (CTL)-mediated tumor cell lysis,
which may lead to a reduction in tumor growth. The binding of AK131 to CD73 inhibits
the activity of CD73. This prevents CD73-mediated conversion of extracellular adenosine
monophosphate (AMP) to adenosine and the adenosine-mediated suppression of lymphocyte
activity and trafficking. This increases the activity of CTLs, activates macrophages
and reduces the activity of both myeloid-derived suppressor cells (MDSCs) and regulatory
T-lymphocytes (Tregs). By abrogating the inhibitory effect on the immune system and
enhancing the CTL-mediated immune response against cancer cells, tumor cell growth
is decreased. The binding of AK131 to CD73 may also promote B-cell activation and
proliferation, thereby further enhancing anti-tumor immune responses. 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 PD-L1 and/or PD-L2; it plays an important role in tumor
evasion from host immunity. CD73, a plasma membrane protein belonging to the 5'-nucleotidase
(NTase) family, is upregulated on a number of cancer cell types and catalyzes the
conversion of extracellular nucleotides, such as AMP, to membrane-permeable nucleosides,
such as adenosine; it plays a key role in adenosine-mediated immunosuppression within
the tumor microenvironment (TME).;
Molecule name : AK 131; AK-131;
NCI Metathesaurus CUI : CL1927675;
Origin ID : C205436;
chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
