Immune checkpoint blockers (ICB) act by reverting the immunosuppressive phenotype of cancer cells, thus allowing host immune system to generate an immune response to the tumor. One of the key mechanisms targeted by ICB is the PD-1/PD-L1 axis, which lies onto the interaction between the programmed-cell death protein 1 and its ligand, overexpressed in several tumor types. This interaction leads to the inhibition of T-cell proliferation and their apoptosis and exhaustion. Anti-PD-1/PD-L1 monoclonal antibodies are now the mainstay of treatment for several advanced stage tumors. Dostarlimab is a novel IgG4 anti-PD-1 antibody which has yielded remarkable results in mismatch-repair deficient endometrial cancer and locally advanced rectal cancer. This product review will illustrate the preclinical development of dostarlimab and its pharmacological characteristics, the clinical trials published so far and the ongoing clinical investigations.

Cicala, C. M., Musacchio, L., Scambia, G., Lorusso, D., Dostarlimab: From preclinical investigation to drug approval and future directions, <<HUMAN VACCINES & IMMUNOTHERAPEUTICS>>, 2023; 19 (1): 1-10. [doi:10.1080/21645515.2023.2178220] [https://hdl.handle.net/10807/232223]

Dostarlimab: From preclinical investigation to drug approval and future directions

Cicala, Carlo Maria;Scambia, Giovanni;Lorusso, Domenica
2023

Abstract

Immune checkpoint blockers (ICB) act by reverting the immunosuppressive phenotype of cancer cells, thus allowing host immune system to generate an immune response to the tumor. One of the key mechanisms targeted by ICB is the PD-1/PD-L1 axis, which lies onto the interaction between the programmed-cell death protein 1 and its ligand, overexpressed in several tumor types. This interaction leads to the inhibition of T-cell proliferation and their apoptosis and exhaustion. Anti-PD-1/PD-L1 monoclonal antibodies are now the mainstay of treatment for several advanced stage tumors. Dostarlimab is a novel IgG4 anti-PD-1 antibody which has yielded remarkable results in mismatch-repair deficient endometrial cancer and locally advanced rectal cancer. This product review will illustrate the preclinical development of dostarlimab and its pharmacological characteristics, the clinical trials published so far and the ongoing clinical investigations.
2023
Inglese
Cicala, C. M., Musacchio, L., Scambia, G., Lorusso, D., Dostarlimab: From preclinical investigation to drug approval and future directions, <<HUMAN VACCINES & IMMUNOTHERAPEUTICS>>, 2023; 19 (1): 1-10. [doi:10.1080/21645515.2023.2178220] [https://hdl.handle.net/10807/232223]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/232223
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