Looking for the Optimal PD-1/PD-L1 Inhibitor in Cancer Treatment: A Comparison in Basic Structure, Function, and Clinical Practice

Abstract

Programmed cell death protein-1/ligand 1 (PD-1/L1) targeted immune checkpoint inhibitors have become the focus of tumor treatment due to their promising efficacy. Currently, several PD-1/PD-L1 inhibitors have been approved for clinical practice with several more in clinical trials. Notably, based on available trial data, the selection of different PD-1/PD-L1 inhibitors in the therapeutic application and the corresponding efficacy varies. Widespread attention then is increasingly raised to the clinical comparability of different PD-1/PD-L1 inhibitors. The comparison of the inhibitors could not only help clinicians make in-depth understanding of them, but also further facilitate the selection of the optimal inhibitor for patients in treatment as well as for future clinical research and the development of new related drugs. As we all know, molecular structure could determine molecular function, which further affects their application. Therefore, in this review, we aim to comprehensively compare the structural basis, molecular biological functions, and clinical practice of different PD-1/PD-L1 inhibitors.

Keywords: PD-1 inhibitors; PD-L1 inhibitors; comparison; differences; efficacy; optimal treatment.

Figure 1

The rationale of PD-1/PD-L1 inhibitors. In tumor tissue, PD-1 interacts with PD-L1 or PD-L2 to mediate significant immune suppression. PD-1/PD-L1 inhibitors binds to corresponding target, thus blocking the PD-1/PD-L1 signaling pathway and markedly enhancing T cell function and the anti-tumor immunity.

Figure 2

The basic structure of IgG. IgG can be divided into two parts including Fab fragment and Fc fragment. Fab fragment plays an important role in antigen recognition and binding while Fc fragment can mediate ADCC, CDC, and ADCP. Besides, Fc fragment can bind to FcRn to protect itself from elimination.