Enhanced binding at fever temperatures of HER2 in complex with trastuzumab and pertuzumab.

Fever follows the administration of trastuzumab and pertuzumab used in HER2-relevant immunotherapy, but is often eliminated in clinical practice. This work explores the role of temperature (37-39°C) in the formation of immune complexes between HER2 with either trastuzumab or pertuzumab or with both antibodies. Using molecular dynamics simulations and free energy calculations, the binding between HER2 and these immunotherapeutic monoclonal antibodies was investigated at different temperatures. Trastuzumab and pertuzumab present the highest binding free energy to HER2 at febrile temperatures (39°C), or when HER2 is in complex with both antibodies. Performing molecular dynamics simulations under fever temperatures may be important for delineating their role in enhancing the binding affinity of mature antibodies used in immunotherapy.