Polzastobart

Polzastobart (JTX-8064) is a humanized monoclonal antibody targeting LILRB2 that blocks its interaction with ligands and MHC class I molecules. Polzastobart blocks LILRB2-mediated immunosuppressive signaling, promotes the polarization of macrophages toward a pro-inflammatory phenotype, and enhances their production of pro-inflammatory cytokines. Polzastobart is a macrophage immune checkpoint inhibitor. Polzastobart exhibits antitumor activity and is being investigated for the treatment of refractory solid tumors.

Polzastobart blocks the binding of LILRB2 to its homologous ligands, including classical and non-classical MHC molecules. In vitro, Polzastobart drives human macrophages and dendritic cells to polarize toward immunostimulated phenotypes. Polzastobart binds to purified LILRB2 protein with high affinity. The Kd value is 3.18 ± 0.083 nmol/L, the association rate constant is 6.58 × 105 M-1 s-1, and the dissociation rate constant is 2.09 × 10-3 s-1.
Polzastobart increases LPS-induced TNF-α production and suppresses the production of the immunosuppressive cytokine IL10 in a dose-dependent manner. The EC50 concentration of TNF-α production is 0.01356 nmol/L, and the IC50 concentration of IL10 production is 0.01425 nmol/L. [1]
Polzastobart has been shown to enhance the production of pro-inflammatory cytokines in macrophages. [2]

Polzastobart causes human macrophages to repolarize from M2 (inhibitory) to M1 (pro-inflammatory) phenotype and enhances anti-tumor immunity in mouse models. [2]

Human

Monoclonal

Unconjugated