<?xml version="1.0"?>
<!-- FILE : kirschner_model_1998.xml
CREATED : 28th March 2004
LAST MODIFIED : 28th March 2004
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Kirschner and Panetta's 1998 mathematical model of the immunotherapy of the tumour-immune interaction.
CHANGES:
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<article>
<articleinfo>
<title>Modelling Immunotherapy of the Tumour-Immune Interaction</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This model has been recoded using the nondimensionalized equations. This was suggested by the author to help with solving the problem, due to its very stiff nature. Some but not all output from the paper can be reproduced by this model. Values of s1 and s2 have been set to zero to represent a non-treatment situation. A value of 0.02 has been given to the variable c, which defines the antigenicity of the tumour, to represent the middle of the range given for this parameter. The model may be re-parameterised to give other relevant outputs, for example, if s1 is greater than 0 while s2 equals 0, the model can simulate adoptive cellular immunotherapy. The model will not run in COR due to time being defined as dimensionless.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
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.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Modeling immunotherapy of the tumor-immune interaction, Denise Kirschner and John Carl Panetta, 1998,
<emphasis>Journal of Mathematical Biology</emphasis>, 37, 235-252. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/9785481">PubMed ID: 9785481</ulink>
</para>
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<title>reaction diagram</title>
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<caption>
A schematic diagram of the interactions between the effector T cells, the tumour cells, and the cytokine interleukin-2 (IL-2).
</caption>
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</sect1>
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The values for these variables are not given in the paper but those given here appear to be reasonable.</rdf:value><modified xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#7c6a9638-372d-4191-b362-847260b56871"/></modified></rdf:Description><rdf:Description rdf:about="rdf:#57743721-d471-4520-8b80-77dec871ac34"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Richard</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">James</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lawson</Family></rdf:Description><rdf:Description rdf:about="rdf:#5192b9e4-77d0-4709-b492-31dab6084014"><Journal xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#d5895ccf-7b31-433b-adaf-969aa226549a"/></Journal><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#b3e2cb6a-293f-4847-8a12-d7c5443f4efc"/></creator><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Modeling immunotherapy of the tumor-immune interaction</title><first_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">235</first_page><volume xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">37</volume><last_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">252</last_page><issued xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#ec750012-9407-451c-b78a-a6100474e6f7"/></issued></rdf:Description><rdf:Description rdf:about="rdf:#a24cbc57-027d-4fba-95f1-1563ba0d8fc1"><cmeta:modifier><rdf:Description rdf:about="rdf:#099ad25d-111d-475d-9e17-54d7846d5f5a"/></cmeta:modifier><rdf:value xml:lang="en">Rewrote the model to use the non-dimensionalised equations (given in the paper.) Non-dimensionalized all variables so model will now meet unit tests. Author suggested that NDization helps with solving the model, which is very stiff.</rdf:value><modified xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#aa603c82-784d-4e82-8640-486a45092616"/></modified></rdf:Description><rdf:Description rdf:about="#x"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">non-dimensionalized form of T - effector T cells</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">x</title></rdf:Description><rdf:Description rdf:about="rdf:#ee35e1db-6e21-4c20-9a7c-e9d2929721b7"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Richard</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">James</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lawson</Family></rdf:Description><rdf:Description rdf:about="rdf:#8682124e-fef8-42e5-940c-d24295a30e39"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Denise</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Kirschner</Family></rdf:Description><rdf:Description rdf:about="rdf:#e0fcad6f-4780-45b3-a73d-e4b73dbcb28b"><Pubmed_id xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">9785481</Pubmed_id><JournalArticle xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#5192b9e4-77d0-4709-b492-31dab6084014"/></JournalArticle></rdf:Description><rdf:Description rdf:about="rdf:#d0a4817b-aeb5-491c-9484-3091f76cd007"><rdf:value xml:lang="en">This model has been recoded using the nondimensionalised equations. This was suggested by the author to help with solving the problem, due to its very stiff nature. Some but not all output from the paper can be reproduced by this model. Values of s1 and s2 have been set to zero to represent a non-treatment situation. A value of 0.025 has been given to the variable c, which defines the antigenicity of the tumour, to represent the middle of the range given for this parameter. The model may be re-parameterised to give other relevant outputs, for example, if s1 is greater than 0 while s2 equals 0, the model can simulate adoptive cellular immunotherapy.
This version is known to run in PCEnv and is likely to run in COR, and passes all unit checks (being non-dimensionalised). This version is able to produce some of the figures in the paper. Contact with the model author re: some parameters is pending.</rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#1d98e31d-114d-4c82-8628-070b4de48817"/></creator></rdf:Description><rdf:Description rdf:about="rdf:#0fd04615-e14d-4441-854c-9420d4e6d420"><rdf:value xml:lang="en">This is the CellML description of Kirschner and Panetta's 1998 mathematical model of the immunotherapy of the tumour-immune interaction.</rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#3831f29c-be0d-437a-97b8-146d424193b4"/></creator></rdf:Description><rdf:Description rdf:about="rdf:#a6341a62-d49f-4c5e-b052-b471cda300fe"><rdf:_7 xml:lang="en">cytokine</rdf:_7><rdf:_1 xml:lang="en">tumour</rdf:_1><rdf:_2 xml:lang="en">immunology</rdf:_2><rdf:_6 xml:lang="en">T cell</rdf:_6><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Bag"/></rdf:type><rdf:_3 xml:lang="en">pharmacology</rdf:_3><rdf:_5 xml:lang="en">t cell</rdf:_5><rdf:_4 xml:lang="en">signal transduction</rdf:_4></rdf:Description><rdf:Description rdf:about="rdf:#aa2df9c4-c17a-498e-ba4f-f2c88bb16e2b"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#aab9ea91-efce-4b60-b249-f52a1dfd9b37"/></N><EMAIL xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#96eb2588-5f64-404f-9f59-a8c820ece1f9"/></EMAIL><ORG xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#e154f7c9-084c-4a76-9f36-3b09016588cb"/></ORG></rdf:Description><rdf:Description rdf:about="#kirschner_1998"><simulation xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:about="rdf:#$l+h6c"/></simulation><cmeta:comment><rdf:Description rdf:about="rdf:#0fd04615-e14d-4441-854c-9420d4e6d420"/></cmeta:comment><cmeta:bio_entity xml:lang="en">T lymphocyte</cmeta:bio_entity><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Kirschner and Panetta's 1998 mathematical model of the immunotherapy of the tumour-immune interaction.</title><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#e0fcad6f-4780-45b3-a73d-e4b73dbcb28b"/></reference><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#3649cadb-1733-41d3-babc-4cb88ab82afd"/></reference></rdf:Description><rdf:Description rdf:about="rdf:#494c01d2-f107-40e8-9dfe-f83a72d89410"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Carl</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">John</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Panetta</Family></rdf:Description><rdf:Description rdf:about="rdf:#a93f969b-64c7-41e8-8894-9898349f32b2"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#494c01d2-f107-40e8-9dfe-f83a72d89410"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#d5895ccf-7b31-433b-adaf-969aa226549a"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Journal of Mathematical Biology</title></rdf:Description><rdf:Description rdf:about="rdf:#$l+h6c"><boundIntervals xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:about="rdf:#$m+h6c"/></boundIntervals></rdf:Description><rdf:Description rdf:about="rdf:#7c6a9638-372d-4191-b362-847260b56871"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2007-08-02T14:17:42+12:00</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#8d323650-f5e6-4ccc-a38f-58505d923318"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#8682124e-fef8-42e5-940c-d24295a30e39"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="#y"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">non-dimensionalized form of variable T - tumour cells</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">y</title></rdf:Description><rdf:Description rdf:about="rdf:#1d98e31d-114d-4c82-8628-070b4de48817"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">James Lawson</FN></rdf:Description><rdf:Description rdf:about="rdf:#96eb2588-5f64-404f-9f59-a8c820ece1f9"><rdf:value xml:lang="en">c.lloyd@auckland.ac.nz</rdf:value><rdf:type><rdf:Description rdf:about="http://imc.org/vCard/3.0#internet"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#b3e2cb6a-293f-4847-8a12-d7c5443f4efc"><rdf:_1><rdf:Description rdf:about="rdf:#8d323650-f5e6-4ccc-a38f-58505d923318"/></rdf:_1><rdf:_2><rdf:Description rdf:about="rdf:#a93f969b-64c7-41e8-8894-9898349f32b2"/></rdf:_2><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Seq"/></rdf:type></rdf:Description></rdf:RDF></model>
