Crystal structure of PD-1 in complex with an antibody-drug tislelizumab used in tumor immune checkpoint therapy.
Biochem Biophys Res Commun
; 527(1): 226-231, 2020 06 18.
Article
en En
| MEDLINE
| ID: mdl-32446372
ABSTRACT
Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front ß-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Hodgkin
/
Anticuerpos Monoclonales Humanizados
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Receptor de Muerte Celular Programada 1
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Inhibidores de Puntos de Control Inmunológico
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Inmunoterapia
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2020
Tipo del documento:
Article