It has been 13 years since the first patients enrolled into the first-in-human trial evaluating MDX-11061 blocking the interaction between programmed-death 1 (PD-1), expressed in T cells on activation during priming or expansion, and its ligands programmed-death ligands 1 and 2 (PD-L1 and PD-L2), a mechanism of physiologic immune homeostasis restricting anticancer immunity. Since then, no fewer than 6 anti–PD-1 or PD-L1 monoclonal antibodies have garnered regulatory approval in the United States or Europe for the treatment of 11 cancer types as well as cancers harboring defects in their mismatch repair machinery (Box). More than 22 further compounds, predominantly monoclonal antibodies, including bispecific antibodies, oral small molecule inhibitors, and fusion proteins are currently in clinical development (Box), a testament to the importance of this axis as a pervasive mechanism of cancer immune evasion. In addition, opening the debate of sustainability and addressing the World Health Organization priority of achieving universal health coverage, several anti–PD-1/PD-L1 compounds and biosimilars are being developed, generating hopes for affordable and quality products for low- and middle-income countries.2
Zimmermann S, Peters S. Appraising the Tail of the Survival Curve in the Era of PD-1/PD-L1 Checkpoint Blockade. JAMA Oncol. 2019;5(10):1403–1405. doi:10.1001/jamaoncol.2019.2186
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