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...

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Veröffentlicht in:Immunotherapy 2023-09, Vol.15 (13), p.1021-1027
Hauptverfasser: Singh, Puneet K, Stan, Razvan C
Format: Artikel
Sprache:eng
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Zusammenfassung: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. Breast cancer patients may present fever due to the cancer itself, due to treatment with chemotherapy or monoclonal antibody therapy, or after surgery. In this work, the role of febrile temperatures on the activity of two of the most commonly used monoclonal antibodies for breast cancer treatment, trastuzumab and pertuzumab, was investigated. These therapeutic agents benefit from fever in terms of binding to their tumor target, particularly when both antibodies are deployed together, mirroring the clinical benefits of their dual therapy. These results are important because, in clinical practice, fever that accompanies treatment in cancer patients is usually eliminated. As such, further investigations into the positive role of fever-range temperatures in assisting antibody therapy for breast cancer are warranted.
ISSN:1750-743X
1750-7448
DOI:10.2217/imt-2023-0065