Anti-Human PD-1 (Dostarlimab)

PD-1 is a transmembrane protein in the CD28/CTLA-4 subfamily of the Ig superfamily1, 2.

When stimulated via the T cell receptor (TCR), Tregs translocate PD-1 to the cell surface3.

Programmed cell death 1 ligand 1 (PD-L1; CD274; B7H1) and programmed cell death 1 ligand 2 (PD-L2; CD273; B7DC) have been identified as PD-1 ligands1.

PD-1 is co-expressed with PD-L1 on tumor cells and tumor-infiltrating antigen-presenting cells (APCs)2.

Additionally, PD-1 is co-expressed with IL2RA on activated CD4+ T cells3. PD-1 is an immune checkpoint receptor that suppresses cancer-specific immune responses4.

Additionally, PD-1 acts as a T cell inhibitory receptor and plays a critical role in peripheral tolerance induction and autoimmune disease prevention as well as important roles in the survival of dendritic cells, macrophage phagocytosis, and tumor cell glycolysis2.

PD-1 prevents uncontrolled T cell activity, leading to attenuation of T cell proliferation, cytokine production, and cytolytic activities.

Additionally, the PD-1 pathway is a major mechanism of tumor immune evasion, and, as such, PD-1 is a target of cancer immunotherapy2.

Dostarlimab is a humanized monoclonal antibody that acts as a PD-1 receptor antagonist4, 5.

Generated from a mouse hybridoma using SHM-XELTM technology, Dostarlimab was developed for the treatment of various cancers, and in 2021 was approved in the EU and USA for treatment of adult patients with mismatch repair deficient recurrent or advanced endometrial cancer4.

Dostarlimab binds to and inhibits PD-1 and potently blocks interaction with PD-L1 and PD-L2, thus restoring immune function by activating T cells4, 5.

Dostarlimab also acts as a functional antagonist in a human CD4+ mixed lymphocyte reaction assay, leading to increased IL-2 production.