// Created by libAntimony v2.13.0
function Function_for_Tumor_Cell_exponential_growth(r, U)
  r*U;
end

Function_for_Tumor_Cell_exponential_growth is "Function for Tumor Cell exponential growth"

function Function_for_Tumor_Cell_infection(beta, U, V, N)
  beta*U*V/N;
end

Function_for_Tumor_Cell_infection is "Function for Tumor Cell infection"

function Function_for_Tumor_Cell_elimination(k0, c_kill, I, U, T, N)
  (k0 + c_kill*I)*U*T/N;
end

Function_for_Tumor_Cell_elimination is "Function for Tumor Cell elimination"

function Function_for_Infected_Tumor_Cell_death(delta_I, I)
  delta_I*I;
end

Function_for_Infected_Tumor_Cell_death is "Function for Infected Tumor Cell death"

function Function_for_Infected_Tumor_Cell_elimination(k0, c_kill, I, T, N)
  (k0 + c_kill*I)*I*T/N;
end

Function_for_Infected_Tumor_Cell_elimination is "Function for Infected Tumor Cell elimination"

function Function_for_treatment_with_virus(U_V)
  U_V;
end

Function_for_treatment_with_virus is "Function for treatment with virus"

function Function_for_release_of_virus(alpha, delta_I, I)
  alpha*delta_I*I;
end

Function_for_release_of_virus is "Function for release of virus"

function Function_for_natural_decay_of_virus(delta_V, V)
  delta_V*V;
end

Function_for_natural_decay_of_virus is "Function for natural decay of virus"

function Function_for_Activation_of_T_cells__4_1BBL(C_T, I)
  C_T*I;
end

Function_for_Activation_of_T_cells__4_1BBL is "Function for Activation of T cells; 4-1BBL"

function Function_for_natural_death_of_T_cells(delta_T, T)
  delta_T*T;
end

Function_for_natural_death_of_T_cells is "Function for natural death of T cells"

function Function_for_production_of_T_cells(chi_D, D)
  chi_D*D;
end

Function_for_production_of_T_cells is "Function for production of T cells"

function Function_for_treatment_of_DC(U_D)
  U_D;
end

Function_for_treatment_of_DC is "Function for treatment of DC"

function Function_for_natural_decay_of_DC(delta_D, D)
  delta_D*D;
end

Function_for_natural_decay_of_DC is "Function for natural decay of DC"


model *New_Model()

  // Compartments and Species:
  compartment compartment_;
  species Uninfected_Tumor_Cell_U in compartment_, Infected_Cancer_Cell_I in compartment_;
  species Oncolytic_Adenovirus_V in compartment_, Tumor_targeting_T_cells_T in compartment_;
  species Naive_T_cells_A in compartment_, Dendritic_Cells_D in compartment_;
  species $Total_cells_N in compartment_, $total_tumor_cells in compartment_;

  // Assignment Rules:
  Total_cells_N := Uninfected_Tumor_Cell_U + Infected_Cancer_Cell_I + Tumor_targeting_T_cells_T;
  total_tumor_cells := Uninfected_Tumor_Cell_U + Infected_Cancer_Cell_I;

  // Reactions:
  Tumor_cell_U_exponential_growth:  => Uninfected_Tumor_Cell_U; compartment_*Function_for_Tumor_Cell_exponential_growth(r, Uninfected_Tumor_Cell_U);
  Tumour_cell_U_elimination: Uninfected_Tumor_Cell_U => ; compartment_*Function_for_Tumor_Cell_elimination(k0, c_kill, Infected_Cancer_Cell_I, Uninfected_Tumor_Cell_U, Tumor_targeting_T_cells_T, Total_cells_N);
  Tumor_Cell_U_infection: Uninfected_Tumor_Cell_U => Infected_Cancer_Cell_I; compartment_*Function_for_Tumor_Cell_infection(beta, Uninfected_Tumor_Cell_U, Oncolytic_Adenovirus_V, Total_cells_N);
  Infected_Tumor_Cell_I_death: Infected_Cancer_Cell_I => ; compartment_*Function_for_Infected_Tumor_Cell_death(delta_I, Infected_Cancer_Cell_I);
  Infected_Tumor_Cell_I_elimination: Infected_Cancer_Cell_I => ; compartment_*Function_for_Infected_Tumor_Cell_elimination(k0, c_kill, Infected_Cancer_Cell_I, Tumor_targeting_T_cells_T, Total_cells_N);
  Treatment_with_virus:  => Oncolytic_Adenovirus_V; compartment_*Function_for_treatment_with_virus(U_V);
  Natural_decay_of_virus: Oncolytic_Adenovirus_V => ; compartment_*Function_for_natural_decay_of_virus(delta_V, Oncolytic_Adenovirus_V);
  Release_of_virus:  => Oncolytic_Adenovirus_V; compartment_*Function_for_release_of_virus(alpha, delta_I, Infected_Cancer_Cell_I);
  Activation_of_T_cells_4_1BBL:  => Tumor_targeting_T_cells_T; compartment_*Function_for_Activation_of_T_cells__4_1BBL(C_T, Infected_Cancer_Cell_I);
  Production_of_T_cells:  => Tumor_targeting_T_cells_T; compartment_*Function_for_production_of_T_cells(chi_D, Dendritic_Cells_D);
  natural_death_of_T_cells: Tumor_targeting_T_cells_T => ; compartment_*Function_for_natural_death_of_T_cells(delta_T, Tumor_targeting_T_cells_T);
  Treatment_with_Dendritic_Cells_D:  => Dendritic_Cells_D; compartment_*Function_for_treatment_of_DC(U_D);
  natural_decay_of_Dendritic_Cells_D: Dendritic_Cells_D => ; compartment_*Function_for_natural_decay_of_DC(delta_D, Dendritic_Cells_D);

  // Events:
  OV_1: at time == 0, t0=false, fromTrigger=false: Oncolytic_Adenovirus_V = Oncolytic_Adenovirus_V + OV_dose;
  OV_2: at time == 2, t0=false, fromTrigger=false: Oncolytic_Adenovirus_V = Oncolytic_Adenovirus_V + OV_dose;
  OV_3: at time == 4, t0=false, fromTrigger=false: Oncolytic_Adenovirus_V = Oncolytic_Adenovirus_V + OV_dose;
  AD_1: at time == 1, t0=false, fromTrigger=false: Dendritic_Cells_D = Dendritic_Cells_D + D0;
  AD_2: at time == 3, t0=false, fromTrigger=false: Dendritic_Cells_D = Dendritic_Cells_D + D0;
  AD_3: at time == 5, t0=false, fromTrigger=false: Dendritic_Cells_D = D0 + Dendritic_Cells_D;

  // Species initializations:
  Uninfected_Tumor_Cell_U = 57.414042;
  Uninfected_Tumor_Cell_U has substance_per_volume;
  Infected_Cancer_Cell_I = 0;
  Infected_Cancer_Cell_I has substance_per_volume;
  Oncolytic_Adenovirus_V = 0;
  Oncolytic_Adenovirus_V has substance_per_volume;
  Tumor_targeting_T_cells_T = 0;
  Tumor_targeting_T_cells_T has substance_per_volume;
  Naive_T_cells_A = 0;
  Naive_T_cells_A has substance_per_volume;
  Dendritic_Cells_D = 0;
  Dendritic_Cells_D has substance_per_volume;
  Total_cells_N has substance_per_volume;
  total_tumor_cells has substance_per_volume;

  // Compartment initializations:
  compartment_ = 1;
  compartment_ has volume;

  // Variable initializations:
  OV_dose = 2.5;
  D0 = 1;
  r = 0.3198;
  beta = 1.008538;
  k0 = 2;
  c_kill = 0.623397;
  delta_I = 1;
  U_V = 0;
  alpha = 3;
  delta_V = 2.3;
  C_T = 1.428064;
  chi_D = 4.901894;
  delta_T = 0.35;
  U_D = 0;
  delta_D = 0.35;

  // Other declarations:
  const compartment_, OV_dose, D0, r, beta, k0, c_kill, delta_I, U_V, alpha;
  const delta_V, C_T, chi_D, delta_T, U_D, delta_D;

  // Unit definitions:
  unit length = metre;
  unit area = metre^2;
  unit volume = 1e-3 litre;
  unit time_unit = time_unit;
  unit substance = 1e-3 mole;
  unit extent = substance;
  unit substance_per_volume = 1e-3 mole / 1e-3 litre;

  // Display Names:
  time_unit is "time";
  compartment_ is "compartment";
  Uninfected_Tumor_Cell_U is "Uninfected Tumor Cell U";
  Infected_Cancer_Cell_I is "Infected Cancer Cell I";
  Oncolytic_Adenovirus_V is "Oncolytic Adenovirus V";
  Tumor_targeting_T_cells_T is "Tumor-targeting T cells T";
  Naive_T_cells_A is "Naive T cells A";
  Dendritic_Cells_D is "Dendritic Cells D";
  Total_cells_N is "Total cells N";
  total_tumor_cells is "total tumor cells";
  OV_1 is "OV 1";
  OV_dose is "OV dose";
  OV_2 is "OV 2";
  OV_3 is "OV 3";
  AD_1 is "AD 1";
  AD_2 is "AD 2";
  AD_3 is "AD 3";
  Tumor_cell_U_exponential_growth is "Tumor cell U exponential growth";
  Tumour_cell_U_elimination is "Tumour cell U elimination";
  Tumor_Cell_U_infection is "Tumor Cell U infection";
  Infected_Tumor_Cell_I_death is "Infected Tumor Cell I death";
  Infected_Tumor_Cell_I_elimination is "Infected Tumor Cell I elimination";
  Treatment_with_virus is "Treatment with virus";
  Natural_decay_of_virus is "Natural decay of virus";
  Release_of_virus is "Release of virus";
  Activation_of_T_cells_4_1BBL is "Activation of T cells;4-1BBL";
  Production_of_T_cells is "Production of T cells";
  natural_death_of_T_cells is "natural death of T cells";
  Treatment_with_Dendritic_Cells_D is "Treatment with Dendritic Cells D";
  natural_decay_of_Dendritic_Cells_D is "natural decay of Dendritic Cells D";

  // CV terms:
  compartment_ property "http://identifiers.org/ncit/C13413"
  compartment_ taxon "http://identifiers.org/taxonomy/10090"
  Uninfected_Tumor_Cell_U hypernym "http://identifiers.org/efo/0000311"
  Uninfected_Tumor_Cell_U hypernym "http://identifiers.org/bto/BTO:0002014"
  Infected_Cancer_Cell_I hypernym "http://identifiers.org/bto/BTO:0002014"
  Infected_Cancer_Cell_I hypernym "http://identifiers.org/efo/0000311"
  Infected_Cancer_Cell_I propertyBearer "http://identifiers.org/ncit/C25401"
  Oncolytic_Adenovirus_V hypernym "http://identifiers.org/ncit/C28373"
  Oncolytic_Adenovirus_V hypernym "http://identifiers.org/ncit/C14179"
  Tumor_targeting_T_cells_T hypernym "http://identifiers.org/ncit/C129906"
  Tumor_targeting_T_cells_T propertyBearer "http://identifiers.org/ncit/C64542"
  Naive_T_cells_A hypernym "http://identifiers.org/ncit/C129906"
  Dendritic_Cells_D hypernym "http://identifiers.org/bto/BTO:0002042"
  Dendritic_Cells_D hypernym "http://identifiers.org/ncit/C12583"
  Total_cells_N parthood "http://identifiers.org/bto/BTO:0002014"
  Total_cells_N parthood "http://identifiers.org/efo/0000311"
  Total_cells_N parthood "http://identifiers.org/ncit/C129906"
  total_tumor_cells hypernym "http://identifiers.org/efo/0000311"
  total_tumor_cells hypernym "http://identifiers.org/bto/BTO:0002014"
  r hypernym "http://identifiers.org/sbo/SBO:0000610"
  delta_I hypernym "http://identifiers.org/sbo/SBO:0000356"
  delta_V hypernym "http://identifiers.org/sbo/SBO:0000356"
  C_T hypernym "http://identifiers.org/sbo/SBO:0000610"
  chi_D hypernym "http://identifiers.org/sbo/SBO:0000610"
  delta_T hypernym "http://identifiers.org/sbo/SBO:0000356"
  delta_D hypernym "http://identifiers.org/sbo/SBO:0000356"
  Tumor_cell_U_exponential_growth hypernym "http://identifiers.org/go/GO:0040007"
  Tumour_cell_U_elimination hypernym "http://identifiers.org/sbo/SBO:0000179"
  Tumor_Cell_U_infection hypernym "http://identifiers.org/go/GO:0019089"
  Infected_Tumor_Cell_I_death hypernym "http://identifiers.org/sbo/SBO:0000179"
  Infected_Tumor_Cell_I_elimination hypernym "http://identifiers.org/sbo/SBO:0000179"
  Treatment_with_virus hypernym "http://identifiers.org/go/GO:0035737"
  Natural_decay_of_virus hypernym "http://identifiers.org/sbo/SBO:0000179"
  Release_of_virus hypernym "http://identifiers.org/sbo/SBO:0000393"
  Activation_of_T_cells_4_1BBL hypernym "http://identifiers.org/go/GO:0051132"
  Production_of_T_cells hypernym "http://identifiers.org/sbo/SBO:0000393"
  natural_death_of_T_cells hypernym "http://identifiers.org/sbo/SBO:0000179"
  Treatment_with_Dendritic_Cells_D hypernym "http://identifiers.org/go/GO:0035737"
  natural_decay_of_Dendritic_Cells_D hypernym "http://identifiers.org/sbo/SBO:0000179"
end

New_Model is "Gevertz2018 - cancer treatment with oncolytic viruses and dendritic cell injections minimal model"

New_Model model_entity_is "http://identifiers.org/biomodels.db/MODEL1909180002",
                          "http://identifiers.org/biomodels.db/BIOMD0000000817"
New_Model property "http://identifiers.org/doid/DOID:1909"
New_Model property "http://identifiers.org/efo/0000311"
New_Model property "http://identifiers.org/ncit/C62713"
New_Model property "http://identifiers.org/bto/BTO:0002014"
New_Model property "http://identifiers.org/mamo/MAMO_0000046"
New_Model property "http://identifiers.org/efo/0000756"
New_Model taxon "http://identifiers.org/taxonomy/10090"
New_Model description "http://identifiers.org/pubmed/30510594"
