Immunology & inflammation QSPTCE/BsAb

T-cell-engager cytokine-release network

Reference paper ↗

A cytokine-network QSP model coupling drug exposure to resting, activated, cytotoxic, and exhausted T cells and to IL-6, IL-10, IL-1beta, IFN-gamma, and TNF-alpha dynamics.

Therapeutic
Blinatumomab and comparator T-cell agonists
Modality
Bispecific antibody / T-cell engager
Target
CD19, CD3, CD28, IL-6R / CD126
Disease
Cytokine-release syndrome
Model type
QSP, TCE/BsAb

Complete model workspace

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Parameters
33
States
11
Equations
11
Derived outputs
46

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blinatumomab 28 ug/day continuous infusion through day 28

How do drug exposure and immune feedback shape T-cell activation and the timing and magnitude of cytokine release? Explore this biological starting configuration through T-cell agonist concentration, Activated T cells, IL-6, IFN-gamma, TNF-alpha.

Starting result

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Starting configuration

Time: 0–672 hour; step 2

InputDefaultAvailable range
Systemic clearance2.1 L/hour1.05–3.15 L/hour
T-cell activation EC501 nM0.5–1.5 nM
Maximum activated T-cell concentration5,000 cell/uL2,500–7,500 cell/uL
Macrophage activation EC5048.6 pg/mL24.3–72.9 pg/mL
IC50 IL-1050 pg/mL25–75 pg/mL

Expected readouts

Drug concentration (nM) · Activated t (cell/uL) · Il 6 (pg/mL) · Ifn gamma (pg/mL) · Tnf alpha (pg/mL)

Adjustable model parameters

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More key parameters (1)

How the model represents the biology

A cytokine-network QSP model coupling drug exposure to resting, activated, cytotoxic, and exhausted T cells and to IL-6, IL-10, IL-1beta, IFN-gamma, and TNF-alpha dynamics.

How do T-cell agonist exposure and immune feedback shape cytokine release?A continuous or initialized T-cell agonist exposure activates a resting-to-activated-to-cytotoxic and exhausted T-cell program. Cytotoxic T cells and an algebraic macrophage signal produce cytokines, while IL-10 suppresses pro-inflammatory production and an optional rescue switch changes IL-6 feedback behavior.BIOLOGY OVERVIEWHow do T-cell agonist exposure and immune feedback shape cytokine release?T-cell agonist inputInfusion or initializedcomparatorAgonist exposureModeled concentration CdrugT-cell programResting, activated, cytotoxic,exhaustedMacrophage signalAlgebraic cytokine-productiondrivePro-inflammatorycytokinesIL-6, IL-1β, IFN-γ and TNF-αIL-10 feedbackSuppresses modeled productionOptional IL-6 feedbackScenario switch includesrescue behaviorPRIMARY READOUTSAgonist concentrationAgonist concentrationActivated T cellsActivated T cellsIL-6IL-6IFN-γIFN-γTNF-αTNF-α

Solid arrows show modeled movement or change; two-headed arrows show reversible exchange; dashed arrows show modulation without material transfer.

Model scope: CD19/CD3/CD28 and IL-6R binding, tissue compartments, dynamic macrophage-cell states, and tocilizumab PK or occupancy are not represented.

Modeled relationships (9)
  • T-cell agonist input → Agonist exposure: input (flow)
  • Agonist exposure → T-cell program: activation (modulation)
  • T-cell program → Pro-inflammatory cytokines: IFN-γ / TNF-α (production)
  • Pro-inflammatory cytokines → Macrophage signal: macrophage drive (modulation)
  • Macrophage signal → Pro-inflammatory cytokines: IL-6 / IL-1β (production)
  • Macrophage signal → IL-10 feedback: IL-10 (production)
  • IL-10 feedback → Pro-inflammatory cytokines: suppression (modulation)
  • Pro-inflammatory cytokines → Optional IL-6 feedback: IL-6 feedback (modulation)
  • Optional IL-6 feedback → Pro-inflammatory cytokines: switchable (modulation)

Modeled relationships: T-cell agonist input to Agonist exposure: input (flow); Agonist exposure to T-cell program: activation (modulation); T-cell program to Pro-inflammatory cytokines: IFN-γ / TNF-α (production); Pro-inflammatory cytokines to Macrophage signal: macrophage drive (modulation); Macrophage signal to Pro-inflammatory cytokines: IL-6 / IL-1β (production); Macrophage signal to IL-10 feedback: IL-10 (production); IL-10 feedback to Pro-inflammatory cytokines: suppression (modulation); Pro-inflammatory cytokines to Optional IL-6 feedback: IL-6 feedback (modulation); Optional IL-6 feedback to Pro-inflammatory cytokines: switchable (modulation).

Primary readouts: Agonist concentration; Activated T cells; IL-6; IFN-γ; TNF-α.

Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID besbassi_2026_crs_qsp_locked_cytokine_network.

Research use only — not for patient-specific prediction or dosing advice.

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