GTOnco™ Cytokine Response Assay Service
Cytokines are critical mediators of communication for the immune system and act on their target cells to induce systemic and/or localized immune responses. Creative Biolabs is a professional service provider in the field of gene therapy-based I-O drugs development and analysis. We offer multiple cytokine response assays to help our clients assess the function of immune cells. The evaluation of cytokines releasing ability, the types and quantity of cytokines secreted by those immune cells is available at GTOnco™ platform.
Cytokine Response Assay Introduction
Cytokine response assay (CRA) is a specialized tool designed to measure the secretion, expression, and functional activity of cytokines in response to biological stimuli such as cancer cells, IO therapy, or co culture of immune cells. Unlike traditional assays such as ELISA, which measures endpoint cytokine concentration, or Western blotting, which detects protein expression, modern CRAs such as GTOnco™) Integrating temporal resolution (tracking cytokine release over time) and contextual relevance (simulating TME using 3D culture or patient derived cells) to capture the full complexity of immune cancer interactions.
Figure 1. CAR T cells target tumor cells and induce the release of cytokines as IFN-γ or TNF-α, which lead to the activation of bystander immune and non-immune cells as monocytes/macrophages, dendritic cells, NK and T-cell, and endothelial cells.1
The Critical Role of Cytokine Response Assay in Immuno-Oncology
The characterization of cytokine response has become the core of immune oncology research and development, providing key insights to supplement traditional therapeutic efficacy indicators. Many studies have shown that different cytokine patterns are associated with specific clinical outcomes, providing opportunities for treatment stratification and personalization. For example, in patients with nasopharyngeal carcinoma, detailed cytokine analysis shows that the levels of IL-4 and IL-10 are elevated, while the levels of IL-2 and IFN - γ are reduced, which is related to the late stage of the disease. The normalization of these cytokines after treatment is associated with improved prognosis. These findings emphasize the prognostic value of comprehensive cytokine assessment and the importance of using robust and validated detection methods that can detect subtle changes in these soluble mediators.
Type 2 Cytokine Response: A Target for Overcoming Resistance to Immune Checkpoint Inhibitors (IO)
The type 2 cytokine response is characterized by the secretion of IL-4, IL-5, IL-10, and IL-13—cytokines that promote humoral immunity and tissue repair but suppress anti-tumor cellular immunity. In IO, the type 2 cytokine response is a key driver of resistance to immune checkpoint inhibitors (ICIs) and CAR-T therapy, and its evaluation is therefore crucial for treatment development.
Mechanisms of Type 2 Cytokine-Mediated Resistance
- M2 macrophage polarization: IL-4 and IL-13 induce macrophages to adopt an M2 phenotype, thereby secreting TGF-β and IL-10 to suppress T cell activity. In breast cancer, M2 macrophage infiltration is associated with a 2.8-fold increased risk of ICI failure (11).
- Treg expansion: IL-10 promotes Treg differentiation, which in turn suppresses CD8+ T cell function by secreting CTLA-4 or IL-10.
- Th2 Cell Differentiation: Type 2 helper T cells (Th2) secrete IL-4/IL-5, shifting the immune response from cytotoxic CD8+ T cells to B cell-mediated humoral immunity, which is ineffective against solid tumors.
GTOnco™'s Role in Analyzing Type 2 Immune Responses
GTOnco™ includes a specialized type 2 cytokine panel (IL-4, IL-5, IL-10, IL-13, TGF-β) for quantifying these immunosuppressive mediators.
Applications
Immunotherapy Development
Evaluate the risk of CRS and other irAEs in biological drugs such as CAR-T cells, bispecific antibodies and immune checkpoint inhibitors. This detection method can comprehensively profile the cytokine storm that may occur after immune activation, and help detect potential safety hazards in advance.
Mechanism Research
By characterizing cytokine responses in detail, explore how novel therapeutic drugs regulate the immune microenvironment. This application is particularly important for understanding the mode of action of immune modulators and their impact on the balance between anti-tumor immunity and immune suppression.
Biomarker Discovery
Identifying cytokine features that can predict treatment response, disease progression, or immune related adverse events. Research has shown that cytokine patterns can serve as valuable biomarkers for patient stratification and personalized treatment.
Combination Therapy Optimization
By evaluating how different therapeutic drugs interact to shape the cytokine microenvironment, a rational combination therapy plan can be designed. This method helps identify synergistic combinations of cytokines that promote and enhance anti-tumor activity.
Core Services at Creative Biolabs
Generally, the peptide antigens presented by antigen-presenting cells (APCs) can be recognized by T-cell receptors (TCRs). This recognition induces the activation of T-cells and a series of functional immune responses, specifically the cytokine production. The ability of cytokines releasing is an important parameter to evaluate the function as well as the efficiency of gene therapy-based I-O drugs, such as the modified T cells transfer. A reasonable range of cytokine release level is able to just activate T cells but not cause cytokine storm. GTOnco™ platform provides high-quality standard methods for our clients to measure the effector cytokines responses, such as enzyme-linked immunospot assay and intracellular cytokine staining assay (ICS) to detect the secretion of Interferon gamma (IFNγ), Interleukin-2 (IL-2) and other cytokines. Based on the requirements of your projects, we will design the most appropriate method to analyze the released cytokines in your I-O drug development.
Features of Our Cytokine Response Assay at GTOnco™ Platform
- Helping predict the cytokine releasing induced by I-O drugs in safety studies.
- Using appropriately designed studies to assess cytokine releasing with immunogenicity assays in response to I-O drugs.
- Accommodating the measurement of any type of cytokines that you may be interested in.
- Comprehensive analysis reports with accurate assay data and other information required.
GTOnco™ Value in Biomedical Discovery
Evaluation of the Efficacy of Cancer Immunotherapy
GTOnco™ The detection can serve as a functional fingerprint for I-O reagents. By quantifying key immunosuppressive factors in TME derived samples, GTOnco™ It is possible to accurately classify tumors as "cold" or "hot", guiding the basic principles of combination therapy (such as combining ICI with cytokine modulators).
Promoting Translational Medicine
GTOnco™ The quantitative data of the platform is crucial for accelerating the discovery and validation of predictive biomarkers. Our platform is capable of verifying such associations on a large scale and in a reproducible manner, enabling pharmaceutical clients to refine their trial stratification strategies and thus increase the likelihood of positive trial results.
Reasons to Choose Creative Biolabs
Technological Excellence
With our outstanding technological advantages, we ensure accurate determination of cytokine levels within different concentration ranges without the need for dilution or concentration of samples.
Comprehensive Panels
Our extensively validated cytokine combination targets key pathways of cancer immunity.
Sample Flexibility
Our team provides expert guidance on the best sample processing practices for each substrate, maximizing data quality while minimizing pre analysis variability.
Regulatory Support
Our quality system includes strict testing and validation, comprehensive quality control procedures, and detailed standard operating procedures to ensure data integrity and repeatability.
Frequently Asked Questions
Q: What quality control measures have we implemented to ensure the reproducibility of testing?
A: Each test includes comprehensive quality control, including standard samples with known cytokine concentrations, blank samples for evaluating background signals, and internal controls for monitoring changes in test performance over time. These controls must meet the predetermined acceptance criteria in order to report sample data. In addition, we participated in external proficiency testing projects to ensure continuous testing accuracy and inter laboratory reproducibility.
Q: A typical GTOnco™ How long does it take for the cytokine response detection project from sample submission to data delivery?
A: For time sensitive projects, we provide expedited processing services, which can take up to 3 working days at the earliest. For large-scale research or customized panel development, the project schedule will be determined during the initial consultation phase to align with the research deadline.
Q: GTOnco™ How to detect potential cross reactivity between similar cytokines?
A: We use highly specific capture and detection antibodies and conduct rigorous cross reaction screening during the detection and development process. In addition, our proprietary microsphere technology ensures minimal optical interference between detection channels. For customized panels, we conducted comprehensive validation to confirm that there was no cross reactivity between all analyte pairs, and we utilized advanced computational algorithms to correct for any potential interference in complex samples.
Q: Can this detection method distinguish between free cytokines and cytokines that bind to soluble receptors?
A: GTOnco™ Detection is mainly used to detect free bioactive cytokines. Although some immunoassays can measure both free and receptor binding forms, our antibodies are selected to preferentially recognize epitopes on free cytokines that represent biologically available fractions. For researchers who are particularly interested in cytokine receptor complexes, we offer specialized detection methods optimized for these complexes.
We're Here to Help — Contact Us!
Creative Biolabs is committed to offering top-quality cytokine response assay to accelerate customer's gene therapy-based I-O drugs development. The GTOnco™ cytokine response assay platform is a pivotal tool in the functional assessment of next-generation I-O therapies. Multiple analysis technology, in vivo study and in vitro study are available at GTOnco™ platform. Please contact us to discuss your demands or to request a proposal.
Reference
- Cosenza M, Sacchi S, Pozzi S. Cytokine release syndrome associated with T-cell-based therapies for hematological malignancies: pathophysiology, clinical presentation, and treatment. International journal of molecular sciences, 2021, 22(14): 7652. https://doi.org/10.3390/ijms22147652 (Distributed under Open Access license CC BY 4.0, without modification.)
