期刊
REVISTA DE INVESTIGACION CLINICA-CLINICAL AND TRANSLATIONAL INVESTIGATION
卷 73, 期 1, 页码 8-16出版社
INST NACIONAL NUTRICION
DOI: 10.24875/RIC.20000341
关键词
PD-1; PD-L1; Therapeutic antibodies; Cancer immunotherapy; Anti-PD-1; Anti-PD-L1
资金
- Consejo Nacional de Ciencia y Tecnologia (CONACYT) [A1-S-18285]
- Catedras CONACYT [639]
PD-1 and PD-L1 play crucial roles in T cell immunosuppression, with therapeutic antibodies targeting them showing broad clinical applications; however, these targeted therapies are not without adverse effects; understanding the structural domains recognized by antibodies can guide the development of new PD-1 and PD-L1 blocking agents.
Programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand-1 (PD-L1), play key roles in the suppression of the cytotoxic activity of T cells. PD-L1 is overexpressed on various types of cancer cells, leading to immune evasion. In the past decade, therapeutic antibodies that target the PD-1/PD-L1 axis have been developed to inhibit the immune suppression triggered by these two proteins. At present, five antibodies (two anti-PD-1 and three anti-PD-L1) have received approval by regulatory agencies in the US and Europe. In this work, we aimed to review their clinical applications and adverse effects. Furthermore, using their reported crystal structures, we discuss the similarities and differences between the PD-1/PD-L1 interface and the epitopes that are recognized by the antibodies. Detailed analyses of the contact residues involved in the ligand-receptor and target-antibody interactions have shown partial overlap. Altogether, the data presented here demonstrate that: (1) in contrast to other therapeutic antibodies, anti-PD-1/PD-L1 has a wide range of clinical applications; (2) these targeted therapies are not exempt from adverse effects; and (3) the characterization of the structural domains that are recognized by the antibodies can guide the development of new PD-1- and PD-L1-blocking agents.
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