Leon-Triana2021 - Competition between tumour cells and dual-target CAR T-cells

  public model
Model Identifier
BIOMD0000001014
Short description
This model of the use of chimeric antigen receptor (CAR)-T cell therapy in the treatment of solid tumours is described in the article:
"Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept"
Odelaisy León-Triana, Antonio Pérez-Martínez, Manuel Ramírez-Orellana and Víctor M. Pérez-García
Cancers 2021, 13, 703.; doi: 10.3390/cancers13040703

Comment:
This is the second mathematical model, derived from equations 3 to 6, used in the paper.
Reproduction of Figure 5b was achieved by setting alpha_1 = 0.183, in substitution for alpha_1 = 0.2 as quoted in the article.

Abstract:
Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial success against B-cell malignancies, which has led to a growing scientific and clinical interest in extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immunosuppressive tumour microenvironment, which is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using the mathematical model, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study computationally, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. We study in silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive production of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. This strategy could benefit from the combination with PD-1 inhibitors and low tumour loads. Our computational results provide theoretical support for the treatment of different types of solid tumours using T cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD-1 drugs after completion of classical cytoreductive treatments.
Format
SBML (L2V4)
Related Publication
  • Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept.
  • León-Triana O, Pérez-Martínez A, Ramírez-Orellana M, Pérez-García VM
  • Cancers , 2/ 2021 , Volume 13 , Issue 4 , PubMed ID: 33572301
  • Mathematical Oncology Laboratory (MOLAB), Department of Mathematics, Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Avda. Camilo José Cela, 3, 13071 Ciudad Real, Spain.
  • Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial success against B-cell malignancies, which has led to a growing scientific and clinical interest in extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immunosuppressive tumour microenvironment, which is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using the mathematical model, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study computationally, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. We study in silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive production of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. This strategy could benefit from the combination with PD-1 inhibitors and low tumour loads. Our computational results provide theoretical support for the treatment of different types of solid tumours using T cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD-1 drugs after completion of classical cytoreductive treatments.
Contributors
Emilia Chen

Metadata information

hasTaxon
Taxonomy Homo sapiens
hasProperty
occursIn
isDescribedBy

Curation status
Curated


Tags
Name Description Size Actions

Model files

Leon-Triana2021 (eqs 3-6).xml SBML level 2 version 4 representation of the model 47.04 KB Preview | Download

Additional files

Leon-Triana2021 (eqs 3-6).cps COPASI file 78.00 KB Preview | Download
Leon-Triana2021 (eqs 3-6).sedml SEDML file 6.88 KB Preview | Download

  • Model originally submitted by : Emilia Chen
  • Submitted: 12-Jul-2021 18:56:07
  • Last Modified: 20-Jul-2021 15:02:54
Revisions
  • Version: 9 public model Download this version
    • Submitted on: 20-Jul-2021 15:02:54
    • Submitted by: Emilia Chen
    • With comment: Automatically added model identifier BIOMD0000001014
  • Version: 8 public model Download this version
    • Submitted on: 14-Jul-2021 15:33:35
    • Submitted by: Emilia Chen
    • With comment: Model revised without commit message
  • Version: 6 public model Download this version
    • Submitted on: 14-Jul-2021 11:10:27
    • Submitted by: Emilia Chen
    • With comment: Automatically added model identifier BIOMD0000001014
  • Version: 5 public model Download this version
    • Submitted on: 13-Jul-2021 11:08:28
    • Submitted by: Emilia Chen
    • With comment: Model revised without commit message
  • Version: 4 public model Download this version
    • Submitted on: 13-Jul-2021 10:43:47
    • Submitted by: Emilia Chen
    • With comment: Automatically added model identifier BIOMD0000001014
  • Version: 2 public model Download this version
    • Submitted on: 12-Jul-2021 18:56:07
    • Submitted by: Emilia Chen
    • With comment: Automatically added model identifier BIOMD0000001014

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
No records to display
Reactions
No records to display
Curator's comment:
(added: 12 Jul 2021, 18:02:15, updated: 20 Jul 2021, 15:02:48)
Figure 5a of the reference manuscript representing the model in equations 3 to 6 was reproduced using COPASI 4.33.246. The value alpha_1 = 0.183 was used, in substitution for alpha_1 = 0.2 (the value quoted in the manuscript).