Immune Effector Cell associated Neurotoxicity Syndrome (ICANS) Management Solutions

Maximize Success with Creative Biolabs' ICANS Management Solutions

Immune effector cell-associated neurotoxicity syndrome (ICANS) is one of the most serious complications following CAR-T therapy, often manifesting as seizures, encephalopathy, or aphasia. Its unpredictability and variable onset have challenged developers globally. Are you struggling with unpredictable neurotoxicity, delayed CNS symptoms, or difficulty detecting early warning signs? Creative Biolabs integrates cellular, molecular, and functional screening tools to identify neurotoxicity drivers and reduce failure risks across CAR-T pipelines. Our platform helps you control ICANS risk through multi-layered CNS screening, cytokine profiling, and functional neuroimmune assays.

Creative Biolabs delivers a full-service ICANS mitigation workflow including:

• CNS-targeted cytokine release assays
• Real-time BBB disruption and integrity quantification
• Immune cell-neural co-culture systems for cytotoxicity testing
• Transcriptome-based immune signature profiling
• Single-cell RNA sequencing of brain-infiltrating lymphocytes and glial cells
• Functional recovery markers post-CAR exposure (astrocytic calcium flux, neural viability)

We help you prevent costly delays and adverse outcomes by offering mechanistic insight and actionable readouts around ICANS onset. Our services support CAR optimization, safety switch integration, and patient stratification efforts by linking immunotoxic signals to neural outcomes. Whether you're refining a CD19 program or exploring BCMA or GPRC5D targets, our platform identifies CNS liabilities early.

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Strategies

Creative Biolabs employs a comprehensive ICANS control strategy grounded in immunobiology and translational neuroscience:

• Predictive cytokine panels targeting IL-1, IL-6, IFN-γ, and GM-CSF signaling dynamics
• Neuroinflammation profiling using microglia and astrocyte activation readouts
• Single-cell transcriptomic mapping to identify high-risk immune subpopulations
• In vitro BBB permeability models mimicking CNS exposure scenarios
• CNS-directed safety switch evaluations for next-gen CAR designs

Our layered approach targets both primary inflammatory triggers and downstream neurological effects to guide mitigation design.

Our ICANS Management Solutions Service Portfolio

Workflow

1. Target & Construct Intake
   We begin by collecting information about your CAR-T construct design, including scFv structure, signaling domains (e.g., 4-1BB/CD28), target antigens (e.g., CD19, BCMA), and delivery method (e.g., lentiviral, mRNA). This sets the stage for context-specific ICANS assessment.
2. Risk Modeling via Cytokine Induction
   We simulate immune activation using co-cultures or artificial antigen-presenting cells to induce cytokine release. Key neurotoxicity-linked cytokines such as IL-1, IL-6, GM-CSF, and MCP-1 are quantified over time, producing kinetic and threshold data for early ICANS prediction.
3. In Vitro Blood-Brain Barrier (BBB) Assay
   We utilize a human-derived 3D BBB model to evaluate whether your CAR-T construct or secreted cytokines disrupt CNS integrity. TEER, paracellular permeability, and cytokine diffusion metrics provide insight into brain penetration risk.
4. CNS-Immune Cell Co-culture & Damage Readout
   CAR-T cells or cytokine cocktails are applied to neuron-glia co-cultures. We assess neuronal viability, calcium flux, glial morphology, and inflammatory marker expression to identify neurotoxic phenotypes associated with your construct.
5. Single-Cell Neuroimmune Transcriptomics
   Post-treatment, we extract cells from co-culture or in vivo tissues for scRNA-seq. This enables detailed analysis of activated cell subtypes, cytokine-producing populations, and neuroinflammation-related gene signatures at single-cell resolution.
6. Integrated Report & Mitigation Strategy
   We compile all functional, molecular, and cellular data into a comprehensive report. Risk is classified (low/moderate/high), mechanistic drivers are identified, and mitigation suggestions—e.g., switch tuning, cytokine filter design—are provided to guide refinement before clinical use.

Required Starting Materials

• Vector map or plasmid of the CAR construct
• Known cytokine release profile (if applicable)
• Target indication and expected CNS exposure level
• Cell type used (e.g., T, NK, γδ T)
• ICANS risk history (if preclinical data available)

Highlights

Deep Neuroimmune Insight

We integrate CNS-focused cytokine panels, glial activation models, and neuro-immune co-culture systems to deliver a deep understanding of ICANS drivers, helping clients proactively identify and address neurotoxic mechanisms before clinical stages.

Human-Relevant CNS Modeling

Our in vitro blood-brain barrier (BBB) and brain cell co-culture systems are based on human-derived cell types, enabling accurate prediction of CNS responses to CAR-T constructs in physiologically relevant contexts.

Single-Cell Intelligence for Early Detection

We employ single-cell RNA sequencing of immune and neural cells to detect microenvironmental changes, immune infiltration, and neuroinflammation at unprecedented resolution, supporting construct redesign and risk scoring.

Flexible Integration into CAR-T Platforms

Whether you're using lentiviral, mRNA, or non-viral delivery, our ICANS solutions integrate seamlessly with any CAR-T modality and are adaptable to various cell types, including T, NK, and γδ cells.

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Customer Reviews

• Significant neural damage reduction Using Creative Biolabs' ICANS solutions, we identified a high IL-1 and MCP-1 response in our preclinical CD19 CAR-T model and adjusted our cytokine release mitigation strategy accordingly. Jan 2025, Dr. S*** Wong
• Improved BBB safety insight Their BBB model flagged early barrier disruption by our gamma-delta CAR-T platform. It allowed us to redesign the costimulatory domain before clinical escalation. Mar 2025, Dr. R*** Blake
• Actionable single-cell analysis Their single-cell RNA-seq revealed excessive glial activation linked to our construct's persistence. The data helped de-risk our GPRC5D CAR ahead of IND filing. Jun 2025, Dr. L*** Mendez

FAQs

Extended Services

Creative Biolabs provides trusted ICANS mitigation strategies across the CAR-T lifecycle—from early discovery to clinical submission. Our tools accelerate development, reduce neurotoxicity risk, and enhance therapeutic confidence.

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