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Antibody distribution and CCR8 site occupancy

Independently expressed human fixed-context three-region antibody PK and sequential bivalent CCR8 site binding, informed by published scalar estimates. No cell depletion or clinical efficacy is modeled.

Semi-Mechanistic Modeling of S-531011, a Humanized Anti-CCR8 Monoclonal Antibody, for Prediction of CCR8 Receptor Occupancy in Human Tumor Tissues ↗

CPT: Pharmacometrics & Systems Pharmacology

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No antibody control

No-antibody control with no infusions or other dose input over 1008 hours. Free-antibody exposure and occupied-site readouts remain at their zero baseline; receptor renewal maintains baseline sites. No population or cell-depletion prediction.

0–1,008 hour

Scenario details

No antibody control

No-antibody control with no infusions or other dose input over 1008 hours. Free-antibody exposure and occupied-site readouts remain at their zero baseline; receptor renewal maintains baseline sites. No population or cell-depletion prediction.

Readouts

Plasma free antibody · mg/L
Receptor-binding prediction from a deterministic fixed-context mechanism; not cell depletion or measured clinical response.
Tumor free antibody · mg/L
Receptor-binding prediction from a deterministic fixed-context mechanism; not cell depletion or measured clinical response.
Tumor occupied sites percent · dimensionless
Receptor-binding prediction from a deterministic fixed-context mechanism; not cell depletion or measured clinical response.
Central occupied sites percent · dimensionless
Receptor-binding prediction from a deterministic fixed-context mechanism; not cell depletion or measured clinical response.

Study purpose

  • How do the model's key biological readouts change under no antibody control?

Assumptions

  • Interpret patterns within this model and starting configuration; do not treat them as clinical predictions or treatment recommendations.

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Simulation time
h
h
1008 → 168

Time between reported samples.

h
12 → 1

2 changes · Variation 1

Biology

Three free-antibody distribution regions, each with free receptor and one-site or two-site bound complexes; receptor binding is distinct from cell depletion.

Three free-antibody distribution regions, each with free receptor and one-site or two-site bound complexes; receptor binding is distinct from cell depletion.

Model details

15 parameters · 12 states · 12 equations · 8 derived outputs

Classification & API access
Therapeutic
Anti-CCR8 monoclonal antibody fixed parameter context
Modality
Monoclonal antibody
Target
CCR8
Disease / scope
Solid-tumor receptor occupancy context
ParameterDefaultUnitDescription
Antibody molar massantibody_molar_mass148653.5g/molAntibody molar mass coefficient used by the released system of model equations.
Associationassociation11.85L/nmol/hAssociation coefficient used by the released system of model equations.
Baseline cbaseline_c0.0019873nmolBaseline c coefficient used by the released system of model equations.
Baseline pbaseline_p0.0042044nmolBaseline p coefficient used by the released system of model equations.
Baseline tbaseline_t0.000019803nmolBaseline t coefficient used by the released system of model equations.
Dissociationdissociation6.6211/hDissociation coefficient used by the released system of model equations.
Distribution backdistribution_back0.005751/hDistribution back coefficient used by the released system of model equations.
Distribution outdistribution_out0.006951/hDistribution out coefficient used by the released system of model equations.
Free eliminationfree_elimination0.004791/hFree elimination governing first-order loss from the modeled system.
Receptor turnoverreceptor_turnover0.40531/hReceptor turnover coefficient used by the released system of model equations.
Tumor entrytumor_entry0.000017121/hTumor entry coefficient used by the released system of model equations.
Tumor returntumor_return0.0069331/hTumor return coefficient used by the released system of model equations.
Volume cvolume_c2.47LVolume c used to convert modeled amount to concentration in the relevant compartment.
Volume pvolume_p2.99LVolume p used to convert modeled amount to concentration in the relevant compartment.
Volume tvolume_t0.01LVolume t used to convert modeled amount to concentration in the relevant compartment.

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