ISSN: 0034-8376
eISSN: 2564-8896






Anti-PD-1 And Anti-PD-L1 Antibodies as Immunotherapy Against Cancer: A Structural Perspective



Luis Córdova-Bahena, Cátedras Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico City; Department of Pharmacology, Faculty of Medicine, Universidad Autónoma de México (UNAM), Mexico City; Peripheral Research Unit in Translational Biomedicine, Faculty of Medicine, UNAM, and Centro Médico Nacional 20 de noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Mexico City, Mexico
Marco A. Velasco-Velázquez, Department of Pharmacology, Faculty of Medicine, Universidad Autónoma de México (UNAM), Mexico City; Peripheral Research Unit in Translational Biomedicine, Faculty of Medicine, UNAM, and Centro Médico Nacional 20 de noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Mexico City, Mexico


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.



Keywords: PD-1. PD-L1. Therapeutic antibodies. Cancer immunotherapy. Anti-PD-1. Anti-PD-L1.