Structural biology of PD-1/PD-L1 immune checkpoint receptor

Cancer cells avoid and suppress the immune responses through activation of inhibitory immune checkpoints. Blocking the activities of PD-1/PD-L1 or CTLA-4 checkpoints with monoclonal antibodies, and thus restoring T-cell function, has delivered breakthrough therapies against cancer in the recent years. This talk will discuss the basic biology behind the immune checkpoints with the focus on PD-1/PD-L1 system and current therapeutic opportunities. The structural biology of PD-1/PD-L1 will be discussed in more detail based on our results. The development of small molecule inhibitors of PD-1/PD-L1 interaction lags behind that of antibodies. Structural basis for blocking the PD-1/PD-L1 interaction by small molecules (BMS compounds) based on a crystal structure of the first small molecule inhibitor bound to PD-L1 and how this data facilitates the development of better compounds will be discussed. The utility of BMS compounds in restoring the function of T-cells by abolishing the inhibitory activity of the PD-1/PD-L1 immune checkpoint will be demonstrated. Future perspectives in the development of checkpoint inhibitors will be highlighted.

The host for this seminar is Professor Jennifer Potts