Which cytokine release assay is most effective?

Choosing the correct assay format is critical, and it often hinges on the specific test articles being evaluated. In certain scenarios, utilizing multiple testing formats can be beneficial, and we are equipped to employ the most appropriate formats for your compounds. While there have been early studies indicating that blood-based assays might be less sensitive than PBMC-based assays, our experience suggests otherwise. Our fine-tuned whole-blood assay has demonstrated excellent sensitivity with commercially available drugs that are known to induce cytokine release. Additionally, the minimal handling of whole fresh blood in this assay makes it a particularly appealing option.

Cytokine Release Assay

Creative Biolabs is a forward-looking antibody research institution and service provider who leads the development of this era while offering impeccable services to customers all over the globe. Currently, we offer professional service of cytokine release/secretion evaluation using our world-class technologies and profound knowledge in this field.

The Significance of Cytokine Release Evaluation

One major safety concern for therapeutic antibodies lies in the potential infusion reactions during first-in-human trials. While interacting with the indicated target in vivo, therapeutic antibodies can stimulate innate immune system and cause acute and massive cytokine release within minutes. This cytokine release or cytokine storm syndrome, which can be characterized as fever, headache, bronchospasm, hypertension, and even cardiac arrest, represents one of the most malignant side effects of biotherapeutics. Animal tests failed to be fully predictive, thus in vitro cytokine release assays are extremely significant for assessing and avoiding such fatal risks before first-in-human trials. Cytokine release potential is considered as a crucial part for regulatory agencies (i.e. FDA, EMA) in prior to investigational new drug applications (IND) hearings.

Fig.1 Proposed pathomechanism of CRS. (Shimabukuro-Vornhagen, et al., 2018) Fig.1 The mechanism of cytokine release syndrome.^{1, 2}

Our Cytokine Release Evaluation Service: One-stop Comprehensive Service

Equipped with our state-of-the-art techniques and extensive experience, Creative Biolabs offers this unique opportunity for our worldwide clients to adopt high-standard cytokine release evaluating service. Our featured cytokine release assay platform is specially designed by seasoned researchers and is flexible to meet various custom demands and expectations.

Comprehensive menu of cytokine types: we provide a wide range of different cytokines (over 200) that are available to be tested. In addition to regulatory agencies-recommended cytokines including IL-2, IL-4, IL-6, IL-8, IL-10, TNFα, and IFNγ, we can involve any other cytokines of interest upon request, and design an optimal assay panel.
Test system: we can perform this assay with both human PBMCs or specific cell lines. For PBMCs (recommended), we can recruit an indicated number of qualified donors (at least 4), healthy or diseased, to match custom project needs. Fresh whole blood samples will be sourced, and each sample will be undiluted to maximize assay sensitivity.
Antibody exposure: antibody candidates will be incubated with PBMCs or cells with a broad spectrum of concentrations to cover the peak range in vivo. Usually, we start with a trace amount of exposure and end up with sufficiently high concentrations. Besides, the manner to present the testing antibodies is also of great significance. We will consult customers to formulate a most appropriate presentation format.
Measurement techniques: after stimulated by testing antibodies for indicated time, we will harvest the serum and further measure cytokine secretion levels. Creative Biolabs provides multiple techniques, including ELISA. Our well-established technology system can offer high sensitivity, accuracy, and consistency.
Comparable controls: to make sure the evaluation is working properly, we apply comparable control compounds: positive control , which frequently causes cytokine release, and negative control, which has a rather low incidence of infusion reactions.
Data outcome: by the end, comprehensive assay reports will be delivered. Our assay will be conducted under strict FDA/EMA guidelines, thereby we can generate convincing reports in an appropriate format for future IND filings.

Customer Review

Xi*****u

I reached out to Creative Biolabs to assess the cytotoxicity induced by my CD276-targeted antibody using their cytokine release assay service. They customized the experimental plan to fit my specific requirements and provided the results within two weeks. Upon review, I found their findings to be highly accurate and consistently reproducible, aligning perfectly with my own verification tests. Additionally, I was particularly impressed by the comprehensiveness and standardization of the report they delivered, which included all the information I needed.

Frequently Asked Question

Q1: Which cytokine release assay is most effective?
A1: Choosing the correct assay format is critical, and it often hinges on the specific test articles being evaluated. In certain scenarios, utilizing multiple testing formats can be beneficial, and we are equipped to employ the most appropriate formats for your compounds. While there have been early studies indicating that blood-based assays might be less sensitive than PBMC-based assays, our experience suggests otherwise. Our fine-tuned whole-blood assay has demonstrated excellent sensitivity with commercially available drugs that are known to induce cytokine release. Additionally, the minimal handling of whole fresh blood in this assay makes it a particularly appealing option.

Creative Biolabs' impeccable cytokine release assessment service offers a powerful approach to manage potential risks of infusion reactions. Researchers can design much safer schemes during first-in-human trials according to the proper evaluation of risk liabilities. For instance, a lower starting dose can be applied, or antihistamines and steroids can be administered. Experienced scientists in Creative Biolabs will work closely with you step by step to satisfy every specific demand. For more detailed information, please feel free to contact us or directly sent us an inquiry.

References

Shimabukuro-Vornhagen, Alexander, et al. "Cytokine release syndrome." Journal for immunotherapy of cancer 6 (2018): 1-14.
under Open Access License CC BY 4.0, without modification.