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        <pre>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.</pre>
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      <reaction id="CARTcell_proliferation" metaid="COPASI10" name="CARTcell_proliferation" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI10">
              <bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/sbo/SBO:0000393"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/go/GO:0042098"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI10">
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:go:GO:0042098"/>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:sbo:SBO:0000393"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfProducts>
          <speciesReference species="CAR_T_cells" stoichiometry="1"/>
        </listOfProducts>
        <listOfModifiers>
          <modifierSpeciesReference species="Leukaemic_B_cells"/>
          <modifierSpeciesReference species="B_cells_healthy"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Rate_Law_for_CARTcell_proliferation </ci>
                <ci> rho_C </ci>
                <ci> Leukaemic_B_cells </ci>
                <ci> B_cells_healthy </ci>
                <ci> CAR_T_cells </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="CARTcell_death" metaid="COPASI11" name="CARTcell_death" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI11">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/go/GO:0008219"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI11">
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:go:GO:0008219"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference species="CAR_T_cells" stoichiometry="1"/>
        </listOfReactants>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Rate_Law_for_CARTcell_death </ci>
                <ci> tao_C </ci>
                <ci> CAR_T_cells </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Leukaemia_proliferation" metaid="COPASI12" name="Leukaemia_proliferation" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI12">
              <bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/sbo/SBO:0000393"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/ncit/C28378"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI12">
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:ncit:C28378"/>
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:sbo:SBO:0000393"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfProducts>
          <speciesReference species="Leukaemic_B_cells" stoichiometry="1"/>
        </listOfProducts>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Rate_Law_for_Leukaemia_proliferation </ci>
                <ci> rho_L </ci>
                <ci> Leukaemic_B_cells </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Leukaemia_death" metaid="COPASI13" name="Leukaemia_death" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI13">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/go/GO:0008219"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI13">
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:go:GO:0008219"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference species="Leukaemic_B_cells" stoichiometry="1"/>
        </listOfReactants>
        <listOfModifiers>
          <modifierSpeciesReference species="CAR_T_cells"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Rate_Law_for_Leukaemia_death </ci>
                <ci> alpha </ci>
                <ci> Leukaemic_B_cells </ci>
                <ci> CAR_T_cells </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
      <reaction id="Bcell_death" metaid="COPASI14" name="Bcell_death" reversible="false">
        <annotation>
          <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
            <rdf:Description rdf:about="#COPASI14">
	<bqbiol:isVersionOf>
	<rdf:Bag>
	<rdf:li rdf:resource="http://identifiers.org/go/GO:0008219"/>
	</rdf:Bag>
	</bqbiol:isVersionOf>
	</rdf:Description>
	
	
	
	
          </rdf:RDF>
          <COPASI xmlns="http://www.copasi.org/static/sbml">
            <rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
              <rdf:Description rdf:about="#COPASI14">
                <CopasiMT:isVersionOf rdf:resource="urn:miriam:go:GO:0008219"/>
              </rdf:Description>
            </rdf:RDF>
          </COPASI>
        </annotation>
              <listOfReactants>
          <speciesReference species="B_cells_healthy" stoichiometry="1"/>
        </listOfReactants>
        <listOfModifiers>
          <modifierSpeciesReference species="CAR_T_cells"/>
        </listOfModifiers>
        <kineticLaw>
          <math xmlns="http://www.w3.org/1998/Math/MathML">          
            <apply>
              <times/>
              <ci> compartment </ci>
              <apply>
                <ci> Rate_Law_for_Bcell_death </ci>
                <ci> alpha </ci>
                <ci> B_cells_healthy </ci>
                <ci> CAR_T_cells </ci>
                <ci> tao_B </ci>
              </apply>
            </apply>
          </math>
                </kineticLaw>
      </reaction>
    </listOfReactions>
  </model>
</sbml>