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A Biomathematical Model of Tumor Response to Radioimmunotherapy with PDL1 and CTLA4

Gonzalez Crespo, I; Gomez Caamano, A; Lopez Pouso, O; Fenwick, JD; Pardo-Montero, J; (2022) A Biomathematical Model of Tumor Response to Radioimmunotherapy with PDL1 and CTLA4. IEEE/ACM Transactions on Computational Biology and Bioinformatics 10.1109/TCBB.2022.3174454. (In press). Green open access

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Abstract

There is evidence of synergy between radiotherapy and immunotherapy. Radiotherapy can increase liberation of tumor antigens, causing activation of antitumor T-cells. This effect can be boosted with immunotherapy. Radioimmunotherapy has potential to increase tumor control rates. Biomathematical models of response to radioimmunotherapy may help on understanding of the mechanisms affecting response, and assist clinicians on the design of optimal treatment strategies. In this work we present a biomathematical model of tumor response to radioimmunotherapy. The model uses the linear-quadratic response of tumor cells to radiation (or variation of it), and builds on previous developments to include the radiation-induced immune effect. We have focused this study on the combined effect of radiotherapy and PDL1/CTLA4 therapies. The model can fit preclinical data of volume dynamics and control obtained with different dose fractionations and PDL1/CTLA4. A biomathematical study of optimal combination strategies suggests that a good understanding of the involved biological delays, the biokinetics of the immunotherapy drug, and the interplay between them, may be of paramount importance to design optimal radioimmunotherapy schedules. Biomathematical models like the one we present can help to interpret experimental data on the synergy between radiotherapy and immunotherapy, and to assist in the design of more effective treatments.

Type: Article
Title: A Biomathematical Model of Tumor Response to Radioimmunotherapy with PDL1 and CTLA4
Open access status: An open access version is available from UCL Discovery
DOI: 10.1109/TCBB.2022.3174454
Publisher version: https://doi.org/10.1109/TCBB.2022.3174454
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Radioimmunotherapy, radiotherapy, αPDL1, αCTLA4, biomathematical modeling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10161419
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