RT Journal Article
T1 CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models
A1 Leon-Triana, Odelaisy
A1 Sabir, Soukaina
A1 Calvo, Gabriel F.
A1 Belmonte-Beitia, Juan
A1 Chulian, Salvador
A1 Martinez-Rubio, Alvaro
A1 Rosa, Maria
A1 Perez-Martinez, Antonio
A1 Ramirez-Orellana, Manuel
A1 Perez-Garcia, Victor M.
K1 Mathematical modelling
K1 Cancer dynamics
K1 Immunotherapy
K1 Tumour-immune system interactions
K1 Mathematical oncology
K1 Life-span
K1 Remissions
AB 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. 
PB Elsevier
SN 1007-5704
YR 2021
FD 2021-03-01
LK http://hdl.handle.net/10668/18754
UL http://hdl.handle.net/10668/18754
LA en
NO León-Triana O, Sabir S, Calvo GF, Belmonte-Beitia J, Chulián S, Martínez-Rubio Á, et al. CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models. Communications In Nonlinear Science And Numerical Simulation/Communications In Nonlinear Science & Numerical Simulation [Internet]. 1 de marzo de 2021;94:105570
NO This work has been partially supported by the Junta de Comunidades deCastilla-La Mancha (grant number SBPLY/17/180501/000154), the JamesS. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer (Collaborative award 220020450), Junta de Andaluca group FQM-201, Fundacin Española para la Ciencia y la Tecnologa (FECYT, project PR214 from the University of Cádiz) and the Asociacin Pablo Ugarte (APU). OLT is supported by a PhD Fellowship from the University of Castilla-La Mancha research plan.
DS RISalud
RD Apr 11, 2025