Leon-Triana2020 - CAR T-cell therapy in B-cell acute lymphoblastic leukaemia

  public model
Model Identifier
BIOMD0000001011
Short description
This model is based on the publication:
"CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models".
Odelaisy León-Triana, Soukaina Sabir, Gabriel F. Calvo, Juan Belmonte-Beitia, Salvador Chulián, Álvaro Martínez-Rubio, María Rosa, Antonio Pérez-Martínez, Manuel Ramirez-Orellana, Víctor M. Pérez-García
doi: 10.1016/j.cnsns.2020.105570 

Comment:
This model is based on equations (4a)-(4c).

Abstract: 
Immunotherapies use components of the patient immune system to selectively target can- cer 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 extract- ing 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 compart- ments 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 ex- pansion 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.
Format
SBML (L2V4)
Related Publication
  • CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models
  • Odelaisy Leon-Triana, Soukaina Sabir, Gabriel F. Calvo, Juan Belmonte-Beitia, Salvador Chulian, Alvaro Martinez-Rubio, Maria Rosa, Antonio Perez-Martinez, Manuel Ramirez-Orellana, Victor M. Perez-Garcia
  • Communications in Nonlinear Science and Numerical Simulation , 3/ 2020 , Volume 94 , pages: 105570 , DOI: 10.1016/j.cnsns.2020.105570
  • a Department of Mathematics, Mathematical Oncology Laboratory (MOLAB), Universidad de Castilla-La Mancha, Ciudad Real, Spain b Faculty of Sciences, University Mohammed V, Rabat, Morocco c Department of Mathematics, Universidad de Cádiz, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Cádiz, Spain d Translational Research Unit in Paediatric Haemato-Oncology, Haematopoietic Stem Cell Transplantation and Cell Therapy, Hospital Universitario La Paz, Madrid, Spain e Paediatric Haemato-Oncology Department, Hospital Universitario La Paz, Madrid, Spain f Department of Paediatric Haematology and Oncology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Madrid, Spain
  • Immunotherapies use components of the patient immune system to selectively target can- cer 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 extract- ing 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 compart- ments 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 ex- pansion 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.
Contributors
Emilia Chen

Metadata information

hasTaxon
Taxonomy Homo sapiens
occursIn
Brenda Tissue Ontology blood
isDescribedBy
hasProperty

Curation status
Curated


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Model files

Leon-Triana2020 (eqs 4).xml SBML level 2 version 4 representation of the model 30.46 KB Preview | Download

Additional files

Leon-Triana2020 (eqs 4).cps COPASI file 57.34 KB Preview | Download
Leon-Triana2020 (eqs 4).sedml SEDML file 4.17 KB Preview | Download

  • Model originally submitted by : Emilia Chen
  • Submitted: 12-Jul-2021 16:49:17
  • Last Modified: 13-Jul-2021 10:43:37
Revisions
  • Version: 4 public model Download this version
    • Submitted on: 13-Jul-2021 10:43:37
    • Submitted by: Emilia Chen
    • With comment: Automatically added model identifier BIOMD0000001011
  • Version: 2 public model Download this version
    • Submitted on: 12-Jul-2021 16:49:17
    • Submitted by: Emilia Chen
    • With comment: Automatically added model identifier BIOMD0000001011

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Curator's comment:
(added: 12 Jul 2021, 16:47:37, updated: 12 Jul 2021, 16:47:37)
Figure 2 of the reference manuscript representing the model in equations 4a to 4c was reproduced using COPASI 4.33.246.