Optimal control of immune checkpoint inhibitor therapy in a heart-tumour model

Journal article

Abstract:: Autoimmune myocarditis, or cardiac muscle inflammation, is a rare but frequently fatal side–effect of immune checkpoint inhibitors (ICIs), a class of cancer therapies. Despite the dangers that side-effects such as these pose to patients, they are rarely, if ever, included explicitly when mechanistic mathematical modelling of cancer therapy is used for optimization of treatment. In this paper, we develop a twocompartment mathematical model which incorporates the impact of ICIs on both the heart and the tumour. Such a model can be used to inform the conditions under which autoimmune myocarditis may develop as a consequence of treatment. We use this model in an optimal control framework to design optimized dosing schedules for three types of ICI therapy that balance the positive and negative effects of treatment. We show that including the negative side-effects of ICI treatment explicitly within the mathematical framework significantly impacts the predictions for the optimized dosing schedule, thus stressing the importance of a holistic approach to optimizing cancer therapy regimens.

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Language:: English
Keywords:: autoimmune myocarditis

immune checkpoint inhibitors

optimal control

tumour growth
Pubs id:: 2125066
Local pid:: pubs:2125066
Deposit date:: 2025-05-19

Copyright holder:: van der Vegt et al
Rights statement:: © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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