Neurotoxicity related Cytokine Release Assay Service for ICANS Development

Advance Neuro-Immune Safety Testing – Mitigate the Risks of ICANS!

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a serious adverse event frequently observed with CAR-T and T-cell redirecting therapies. It is driven by aberrant cytokine signaling, endothelial activation, and BBB disruption. Preclinical cytokine release assays, especially those incorporating human PBMCs and multiplex cytokine readouts, provide valuable insights into neurotoxicity risk. Publications support the role of IL-6, IFN-γ, IL-1β, and GM-CSF in ICANS onset, underscoring the need for predictive, human-relevant testing models.

Are you facing challenges in identifying neuroinflammatory responses or predicting cytokine-driven toxicity such as ICANS during immunotherapy development? Our Neurotoxicity Related Cytokine Release Assay Service for ICANS Development helps you assess immune-mediated neurotoxicity risks early through high-resolution cytokine profiling, functional PBMC assays, and single-cell immune response characterization.

Creative Biolabs delivers customizable, validated cytokine release assay services with specific relevance to ICANS and neuroimmune safety:

• Quantitative profiling of ICANS-relevant cytokines in supernatants or whole blood.
• Functional characterization of immune cell subsets involved in neuroinflammation.
• Dose-response curves, kinetics, and threshold determination of cytokine induction.
• Inclusion of appropriate controls (anti-CD3, LPS, SEB) and biological replicates.
• Adaptable donor cohort size for exploratory or IND-enabling studies.

Services are delivered with full documentation, statistical summaries, and expert interpretation.

By using primary immune cells and high-sensitivity multiplex platforms, our service identifies cytokine release profiles that may signal neurotoxicity risks early in development. This enables developers to modify drug design, dosing strategies, or safety monitoring plans before clinical exposure.

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Strategies

Creative Biolabs offers ICANS-focused cytokine release assay platforms tailored to immunotherapeutic safety evaluation:

• Donor-Derived PBMC Assays: Fresh or cryopreserved PBMCs from multiple healthy donors used to assess cytokine secretion upon drug exposure.
• Whole Blood-Based Cytokine Testing: Simulates systemic immune activation in a more physiologically intact context.
• Multiplex Cytokine Panels: Targeting key ICANS-associated cytokines, including IL-6, IL-1β, TNF-α, IFN-γ, GM-CSF, and IL-10.
• Intracellular Cytokine Staining (ICS): Enables single-cell resolution of cytokine-secreting immune subsets (e.g., CD4⁺ T cells, CD8⁺ T cells, monocytes).
• Platform Flexibility: ELISA and high-sensitivity MSD formats based on sample volume, panel size, and throughput needs.

Workflow

Required Starting Materials

• Drug/antibody sample (concentration and format details)
• Expected therapeutic concentration range
• Immunogenicity profile or MoA summary

Highlights

• Human-Relevant Safety Prediction: PBMC-based assays better reflect human immune response than traditional animal models, improving translational value.
• ICANS-Specific Cytokine Panels: Focused on IL-6, GM-CSF, and IL-1β, which are implicated in ICANS pathogenesis, allowing early signal detection.
• Single-Cell Resolution: ICS adds precision by pinpointing cytokine-producing subpopulations such as CD14⁺ monocytes or effector T cells.
• Custom Panel Flexibility: Over 200 analytes available for panel customization, covering both pro-inflammatory and regulatory cytokines.
• Platform Versatility: Choose from ELISA or MSD, depending on throughput, sensitivity, and budget.
• Regulatory-Supportive Outputs: Structured reports include dose-dependent responses, CV% across donors, and assay performance metrics—ready for IND submission.

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Publication

CAR-T cell therapy initiates a cascade of immune activation involving T cells, monocytes, macrophages, and endothelial cells, all contributing to the pathogenesis of CRS and ICANS. Upon CAR-T engagement, large quantities of cytokines such as IL-6, IL-1, IFN-γ, GM-CSF, and TNF-α are released, promoting systemic inflammation and blood-brain barrier disruption. Monocyte-derived IL-1 and IL-6 are particularly implicated in ICANS development, while endothelial activation and capillary leak further amplify neurotoxicity. Understanding the interplay between immune effector cells and cytokine networks is essential for designing targeted mitigation strategies in CAR-T therapies.

Fig.1 Overview of immune cells and cytokines driving CRS and ICANS.¹

Customer Reviews

• "ICANS Risk Clarification"
  Using Creative Biolabs' Neurotoxicity Related Cytokine Release Assay Service for ICANS Development in our CAR-T program has significantly improved our understanding of dose-dependent IL-6 and GM-CSF release, helping us mitigate ICANS onset risk in early trials. May 2025, Dr. B***e
• "Customized Panel Value"
  We needed an assay that included IL-1β and neuroinflammation markers, and Creative Biolabs delivered a fully customized panel. The results shaped our internal safety thresholds for candidate selection. February 2025, Prof. Y***n
• "Single-Cell Insight"
  Using Creative Biolabs' ICS-based approach, we identified CD14⁺ monocytes as key cytokine drivers. This insight led to targeted depletion strategies in our preclinical model. July 2025, Dr. M***o

FAQs

Extended Services

Creative Biolabs empowers immunotherapy developers with precise, customizable, and human-relevant cytokine release assay platforms to predict and prevent ICANS.

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Reference

1. Fitzgerald, Julie C., et al. "Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia." Critical care medicine 45.2 (2017): e124-e131. Distributed under Open Access license CC BY 4.0, without modification.