Investigational PD-1 Inhibitor, Tislelizumab, and TGF-β Inhibitor, NIS793

Tislelizumab Mechanism of Action

Tislelizumab is an investigational, humanized IgG4 monoclonal antibody that binds with high affinity to PD-1.1   

Many tumors express large amounts of PD-L1, the ligand for PD-1. Upregulation of PD-L1 leads to T-cell suppression, allowing tumor cells to evade the immune system.2-5    

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Tislelizumab Mechanism of Action

 

 

NIS793 Mechanism of Action

NIS793 is an investigational, fully human monoclonal antibody that binds to transforming growth factor beta (TGFβ)1 and TGFβ2 with high affinity, and TGFβ3 with a lower affinity.6

Genetic alterations of the TGFβ pathway have been implicated in various cancers and are thought to promote tumor initiation, progression, and metastasis.7,8 TGFβ has also been implicated in the development of fibrosis in solid tumors, which has been shown to decrease immune cell infiltration.9 

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NIS793 Mechanism of Action

 

For information about research from Novartis in GI, please visit the Pipeline Navigator.

GI, gastrointestinal; IgG4, immunoglobulin G4; MOA, mechanism of action; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1.

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

MOA data are based on in vitro/in vivo data. 

 

References: 1. Zhang T, Song X, Xu L, et al. Cancer Immunol Immunother. 2018;67(7):1079-1090. doi:10.1007/s00262-018-2160-x. 2. Kala C, Taleuzzaman M, Gilani SJ, et al. In: Beg S, Choudhry H, Souto E., et al. Nanoformulation Strategies for Cancer Treatment. 1st ed. Cambridge, MA: Elsevier; 2021. 3. Tseng D, Schultz L, Pardoll D, et al. In: Niederhuber JE, Armitage JO, Kastan MB, et al. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, PA: Elsevier; 2020. 4. Kalinski P, Basse P. In: Ito F, Ernstoff M. Immune Checkpoint Inhibitors in Cancer. St Louis, MO: Elsevier; 2019. 5. Touboul R, Bonavida B. In: Bonavida B. YY1 in the Control of the Pathogenesis and Drug Resistance of Cancer: A Critical Therapeutic Target. London, UK: Elsevier; 2021. 6. Data on file. NIS793 Investigator's Brochure, Edition 5. Novartis; 2020. 7. Korkut A, Zaidi S, Kanchi RS, et al. Cell Syst. 2018;7:422–437. doi:10.1016/j.cels.2018.08.010. 8. Zavadil J, Cermak L, Soto-Nieves N, et al. EMBO J. 2004;23:1155–1165. doi:10.1038/sj/emboj.7600069. 9. Grauel AL, Nguyen B, Ruddy D, et al. Nat Commun. 2020:11;6315. doi:10.1038/s41467-020-19920-5.