Kirschner1998_Immunotherapy_Tumour

  public model
Model Identifier
BIOMD0000000732
Short description

This a model from the article:
Modeling immunotherapy of the tumor-immune interaction.
Kirschner D, Panetta JC. J Math Biol 1998 Sep;37(3):235-52 9785481 ,
Abstract:
A number of lines of evidence suggest that immunotherapy with the cytokine interleukin-2 (IL-2) may boost the immune system to fight tumors. CD4+ T cells, the cells that orchestrate the immune response, use these cytokines as signaling mechanisms for immune-response stimulation as well as lymphocyte stimulation, growth, and differentiation. Because tumor cells begin as 'self', the immune system may not respond in an effective way to eradicate them. Adoptive cellular immunotherapy can potentially restore or enhance these effects. We illustrate through mathematical modeling the dynamics between tumor cells, immune-effector cells, and IL-2. These efforts are able to explain both short tumor oscillations in tumor sizes as well as long-term tumor relapse. We then explore the effects of adoptive cellular immunotherapy on the model and describe under what circumstances the tumor can be eliminated.

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: Kirschner D, Panetta JC. (1998) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..

To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V4)
Related Publication
  • Modeling immunotherapy of the tumor-immune interaction.
  • Kirschner D, Panetta JC
  • Journal of mathematical biology , 9/ 1998 , Volume 37 , pages: 235-252 , PubMed ID: 9785481
  • Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109-0620, USA.
  • A number of lines of evidence suggest that immunotherapy with the cytokine interleukin-2 (IL-2) may boost the immune system to fight tumors. CD4+ T cells, the cells that orchestrate the immune response, use these cytokines as signaling mechanisms for immune-response stimulation as well as lymphocyte stimulation, growth, and differentiation. Because tumor cells begin as 'self', the immune system may not respond in an effective way to eradicate them. Adoptive cellular immunotherapy can potentially restore or enhance these effects. We illustrate through mathematical modeling the dynamics between tumor cells, immune-effector cells, and IL-2. These efforts are able to explain both short tumor oscillations in tumor sizes as well as long-term tumor relapse. We then explore the effects of adoptive cellular immunotherapy on the model and describe under what circumstances the tumor can be eliminated.
Contributors
Submitter of the first revision: Camille Laibe
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Camille Laibe, Krishna Kumar Tiwari

Metadata information

is (3 statements)
BioModels Database MODEL1006230038
BioModels Database BIOMD0000000732
BioModels Database MODEL1006230038

isDescribedBy (1 statement)
PubMed 9785481

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (1 statement)
Gene Ontology response to tumor cell

hasPart (1 statement)
hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files
Kirschner_1998.xml SBML L2V4 representation of Kirschner1998_Immunotherapy_Tumour 42.55 KB Preview | Download

Additional files
Kirschner_1998.cps COPASI 4.24 (build196) file 66.99 KB Preview | Download
Kirschner_1998.sedml SEDML file 5.34 KB Preview | Download
MODEL1006230038-biopax2.owl Auto-generated BioPAX (Level 2) 1.05 KB Preview | Download
MODEL1006230038-biopax3.owl Auto-generated BioPAX (Level 3) 2.00 KB Preview | Download
MODEL1006230038.m Auto-generated Octave file 2.82 KB Preview | Download
MODEL1006230038.pdf Auto-generated PDF file 133.88 KB Preview | Download
MODEL1006230038.png Auto-generated Reaction graph (PNG) 5.04 KB Preview | Download
MODEL1006230038.sci Auto-generated Scilab file 218.00 Bytes Preview | Download
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MODEL1006230038.vcml Auto-generated VCML file 900.00 Bytes Preview | Download
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MODEL1006230038_urn.xml Auto-generated SBML file with URNs 11.92 KB Preview | Download

  • Model originally submitted by : Camille Laibe
  • Submitted: Jun 23, 2010 10:12:08 AM
  • Last Modified: Jan 29, 2019 3:04:15 PM
Revisions
  • Version: 5 public model Download this version
    • Submitted on: Jan 29, 2019 3:04:15 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000732
  • Version: 2 public model Download this version
    • Submitted on: Jun 25, 2010 1:43:22 PM
    • Submitted by: Camille Laibe
    • With comment: Current version of Kirschner1998_Immunotherapy_Tumour
  • Version: 1 public model Download this version
    • Submitted on: Jun 23, 2010 10:12:08 AM
    • Submitted by: Camille Laibe
    • With comment: Original import of Kirschner1998_Immunotherapy_Tumour

(*) 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
Species Initial Concentration/Amount
Source

empty set 		0.0 mol
Sink

empty set 		0.0 mol
Tumor

EFO:0000616 		1.0 mol
IL2

Interleukin-2 		0.0 mol
Immune cells

macrophage ; natural killer cell ; cytotoxic T-lymphocyte ; Immune Cell 		0.0 mol
Reactions
Reactions Rate Parameters
Source => Immune_cells; Tumor, IL2 COMpartment*(s1+c*Tumor+p1*Immune_cells*IL2/g1) s1 = 0.0 1/d; g1 = 2.0E7 l; c = 0.035 1/d; p1 = 0.1245 1/d
Source => IL2; Immune_cells, Tumor COMpartment*(s2+p2*Immune_cells*Tumor/(g3+Tumor)) g3 = 1000.0 l; s2 = 0.0 1/d; p2 = 5.0 1/d
Immune_cells => Sink COMpartment*mu2*Immune_cells mu2 = 0.03 1/d
Tumor => Sink; Immune_cells COMpartment*a*Immune_cells*Tumor/(g2+Tumor) a = 1.0 1/d; g2 = 100000.0 l
Source => Tumor COMpartment*r2*(1-b*Tumor)*Tumor r2 = 0.18 1/d; b = 1.0E-9 l
IL2 => Sink COMpartment*mu3*IL2 mu3 = 10.0 1/d
Curator's comment:
(added: 28 Jan 2019, 15:02:14, updated: 28 Jan 2019, 15:02:14)
Figure 2A, 2B , 2C and 2D (image included) is reproduced with different c values (as per data given in Literature for each simulation i.e. c=5e-5 (fig2a), c=0.01 (fig2b), c=0.02 (fig2c) and c=0.035 (fig2d). Model is simulated for the time given in Literature for each figure. Model is created and simulation plots were generated using COPASI 4.24 (196). Attached image is an reproduced simulation plot for literature figure 2d. In literature, the y axis value has been scaled to 1E-5 thus plot value seems different but its same (if compared with pre-scaling values).