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Protein & Cell ; (12): 866-877, 2016.
Article Dans Anglais | WPRIM | ID: wpr-757362

Résumé

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.


Sujets)
Humains , Anticorps monoclonaux , Allergie et immunologie , Utilisations thérapeutiques , Anticorps monoclonaux humanisés , Allergie et immunologie , Utilisations thérapeutiques , Antigène CD274 , Allergie et immunologie , Tumeurs , Traitement médicamenteux , Allergie et immunologie , Anatomopathologie , Récepteur-1 de mort cellulaire programmée , Allergie et immunologie , Transduction du signal , Allergie et immunologie , Lymphocytes T , Allergie et immunologie
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