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anti-PD-1/anti-CD73 bispecific antibody AK131

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).
Synonym:anti-CD73/anti-PD-1 bispecific antibody AK131
anti-PD-1/CD73 bispecific antibody AK131
PD-1 x CD73 bispecific antibody AK131
Code name:AK 131
AK-131
AK131
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