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Metaheuristics and Pontryagin’s minimum principle for optimal therapeutic protocols in cancer immunotherapy: a case study and methods comparison

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Abstract

In this paper, the performance appropriateness of population-based metaheuristics for immunotherapy protocols is investigated on a comparative basis while the goal is to stimulate the immune system to defend against cancer. For this purpose, genetic algorithm and particle swarm optimization are employed and compared with modern method of Pontryagin’s minimum principle (PMP). To this end, a well-known mathematical model of cell-based cancer immunotherapy is described and examined to formulate the optimal control problem in which the objective is the annihilation of tumour cells by using the minimum amount of cultured immune cells. In this regard, the main aims are: (i) to introduce a single-objective optimization problem and to design the considered metaheuristics in order to appropriately deal with it; (ii) to use the PMP in order to obtain the necessary conditions for optimality, i.e. the governing boundary value problem; (iii) to measure the results obtained by using the proposed metaheuristics against those results obtained by using an indirect approach called forward-backward sweep method; and finally (iv) to produce a set of optimal treatment strategies by formulating the problem in a bi-objective form and demonstrating its advantages over single-objective optimization problem. A set of obtained results conforms the performance capabilities of the considered metaheuristics.

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Acknowledgements

The authors would like to express their deep gratitude towards the reviewers for their constructive advice, invaluable comments, and support. Furthermore, the authors are grateful to the editorial board for making helpful comments on the work.

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Conceptualization: SSA; methodology: SSA; formal analysis: SSA; Writing–original draft: SSA; supervision: SSA; Writing–review and editing: SSA and AM; Software SSA and AM; validation: SSA; resources: AM; and visualization: AM.

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Correspondence to Sima Sarv Ahrabi.

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This work does not contain any studies with human participants or animals, performed by any of the authors, and any work involving chemicals, procedures or equipment that have any unusual hazards inherent in their use.

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Sarv Ahrabi, S., Momenzadeh, A. Metaheuristics and Pontryagin’s minimum principle for optimal therapeutic protocols in cancer immunotherapy: a case study and methods comparison. J. Math. Biol. 81, 691–723 (2020). https://doi.org/10.1007/s00285-020-01525-7

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  • DOI: https://doi.org/10.1007/s00285-020-01525-7

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