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Chonnam National University Medical School, Hwasun 264, Seoyang-ro, 58128, Republic of Korea

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Razvan C Stan

*Author for correspondence: Tel.: +82 62 220 4000;

E-mail Address: strazvan@jnu.ac.kr

https://orcid.org/0000-0002-9539-6532

Chonnam National University Medical School, Hwasun 264, Seoyang-ro, 58128, Republic of Korea

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Published Online:20 Jun 2023https://doi.org/10.2217/imt-2023-0065

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Abstract

Aim: 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. Materials & methods: Using molecular dynamics simulations and free energy calculations, the binding between HER2 and these immunotherapeutic monoclonal antibodies was investigated at different temperatures. Results: 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. Conclusion: 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.

Plain language summary

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.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 13

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History

Received 14 March 2023

Accepted 25 May 2023

Published online 20 June 2023

Published in print September 2023

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Keywords

Author contributions

Conceptualization; formal analysis; writing: original draft, review and editing; funding acquisition; and supervision: RC Stan. Methodology, formal analysis and writing the original draft: PK Singh.

Acknowledgments

The authors thank Lei Li and Harinda Rajapaksha from Oracle for Research for technical support.

Financial & competing interests disclosure

Funding was provided by the National Research Foundation of Korea, grant 2021R1I1A2059587 (RC Stan). This work was supported by Oracle Cloud credits and related resources provided by the Oracle for Research program, grant CPQ-2615425 (RC Stan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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

Abstract

Plain language summary

References