Journal
COMMUNICATIONS IN NONLINEAR SCIENCE AND NUMERICAL SIMULATION
Volume 94, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.cnsns.2020.105570
Keywords
Mathematical modelling; Cancer dynamics; Immunotherapy; Tumour-immune system interactions; Mathematical oncology
Categories
Funding
- Junta de Comunidades de Castilla-La Mancha [SBPLY/17/180501/0 0 0154]
- James S. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [220020450]
- Junta de Andalucia group [FQM-201]
- Fundacion Espanola para la Ciencia y la Tecnologia (FECYT) [PR214]
- Asociacion Pablo Ugarte (APU)
- University of Castilla-La Mancha research plan
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Immunotherapies, particularly the use of CAR T cells to treat B-cell malignancies, have shown significant success in targeting cancer cells. A mathematical model describing the time response of leukaemias to CAR T cell injection accounts for various biological processes and predicts the dynamics of different compartments post-injection, emphasizing the potential role of competition between leukaemic and CAR T cells in cancer relapses.
Immunotherapies use components of the patient immune system to selectively target cancer cells. The use of chimeric antigenic receptor (CAR) T cells to treat B-cell malignancies-leukaemias and lymphomas- is one of the most successful examples, with many patients experiencing long-lasting full responses to this therapy. This treatment works by extracting the patient's T cells and transducing them with the CAR, enabling them to recognize and target cells carrying the antigen CD19(+), which is expressed in these haematological cancers. Here we put forward a mathematical model describing the time response of leukaemias to the injection of CAR T cells. The model accounts for mature and progenitor B-cells, leukaemic cells, CAR T cells and side effects by including the main biological processes involved. The model explains the early post-injection dynamics of the different compartments and the fact that the number of CAR T cells injected does not critically affect the treatment outcome. An explicit formula is found that gives the maximum CAR T cell expansion in vivo and the severity of side effects. Our mathematical model captures other known features of the response to this immunotherapy. It also predicts that CD19(+) cancer relapses could be the result of competition between leukaemic and CAR T cells, analogous to predator-prey dynamics. We discuss this in the light of the available evidence and the possibility of controlling relapses by early re-challenging of the leukaemia cells with stored CAR T cells. (C) 2020 Elsevier B.V. All rights reserved.
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