Anti-Human PD-1 (Cemiplimab)

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.

Cemiplimab is a fully human, hinge-stabilized (S228P) high affinity anti-PD-1 antibody that potently blocks PD-1 interaction with PD-L1 and PD-L2 ligands and enhances human primary T-cell responses in vitro5.

Cemiplimab was generated using VelocImmune knock-in mice immunized with recombinant human PD-1-mFc protein containing the PD-1 extracellular domain (amino acids 1-167) and the Fc portion of mouse IgG2a.

Splenocyte-derived hybridomas were screened for human monoclonal antibody reactivity to recombinant human PD-1-hFc (extracellular domain of human PD-1 fused to human IgG1 Fc).

Cemiplimab is the first approved treatment in the United States and EU for patients with locally advanced or metastatic cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiotherapy6.