Tislelizumab (BGB-A317; Anti–PD-1 Monoclonal Antibody)

Proposed Mechanism of Action

Tislelizumab is a monoclonal antibody against programmed cell death protein 1 (PD-1), an immune checkpoint protein that inhibits T-cell response.2 Preclinical studies suggest that tumors may upregulate expression of PD-1 ligands (PD-L1 and PD-L2) as a mechanism of immune resistance.2 Blocking the binding of PD-L1 and PD-L2 to PD-1 may restore the T-cell–mediated antitumor response.3

Some preclinical study results have suggested that anti–PD-1 antibodies bound to PD-1 on T cells may also bind to Fc gamma receptors (FCɣRs) on macrophages, which can lead to phagocytosis of the T cell which may compromise antitumor activity.1,4 Anti–PD-1 antibodies can be designed to potentially minimize FCɣR binding.1,4

 

Tislelizumab (BGB-A317) by Disease State

Tislelizumab (BGB-A317) in Solid Tumors

  • Phase 3 Solid Tumors

Rationale for Clinical Development

Studies have shown that PD-1 ligands are commonly upregulated in many tumor types, including solid tumors.2 Preclinical data have suggested that tislelizumab blocks PD-L1 from binding to PD-1 and that this blockade resulted in antitumor activity in a xenograft mouse model.1

 

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

Tislelizumab (BGB-A317), an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, is being developed in collaboration with BeiGene, Ltd.

 

References

  1. Zhang T, et al. Cancer Immunol Immunother. 2018. [Epub ahead of print]. PMID: 29687231
  2. Pardoll DM. Nat Rev Cancer. 2012;12:252-264. PMID: 22437870
  3. Iwai Y, et al. Proc Natl Acad Sci U S A. 2002;99:12293-12297. PMID: 12218188
  4. Dahan R, et al. Cancer Cell. 2015;28:285-295. PMID: 26373277