CRS Preclinical In Vivo Assay Service

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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Creative Biolabs has accumulated rich experience through years of continuous exploration of tumor immunity and hereby launches the cytokine release syndrome (CRS) in vivo detection platform to help customers monitor CRS in CAR-T therapy to mitigate or prevent the formation of cytokine storms.

Background Our Service WorkflowHighlights

Background

Although there is a high response rate after CAR-T cell infusion, safety concerns limit the use of CAR-T cell therapy. CRS is the most common immune-mediated toxicity in CAR-T cell therapy. Adverse responses of CRS are usually fever and constitutional symptoms, including stiffness, malaise, and anorexia. In addition, CRS can also cause systemic inflammation in some severe cases, including hypoxia, hypotension, organ dysfunction, etc. However, if the signs and symptoms of CRS are recognized and treated promptly, organ dysfunction can be prevented or reversed in most patients.

Fig.1 Cellular responses in CRS.¹

Our Service

Creative Biolabs monitors the levels and changes of each cytokine associated with CRS through a combination of in vivo models and multiple in vitro cytokine analysis methods.

In Vivo Model

Brief Description

Creative Biolabs offers both syngeneic and xenograft models to help you achieve preclinical in vivo testing.

The syngeneic model is divided into (1) autologous transplantation, (2) allogeneic transplantation, and (3) allogeneic transplantation.

The xenograft model is divided into (1) cell line-derived xenograft (CDX) models, and (2) patients-derived xenograft (PDX) models.

All of the models we offered are performed strictly to the standard, using approved positive controls for dose-dependent testing. In addition, we can provide customized in vivo models for your project to meet your different needs in CAR-T cell therapy. You can click here to learn more about animal models.

Fig.2 Preclinical in vivo mouse models of tumors.²

Animal Model Type

Mouse, rat, rabbit, non-human primate (NHP) models and more.

Cytokine Release Assay Service

Brief Description

In addition to in vivo models, Creative Biolabs offers a variety of cytokine analysis methods, including ELISA/CBA, intracellular cytokine staining (ICS), and ELIspot. By combining in vivo models with in vitro analysis methods, the level and changes of each cytokine can be monitored, which is conducive to early diagnosis, timely intervention and efficacy monitoring of CRS after CAR-T therapy.

Published Data

Fig.3 CAR-T cytokine levels in peripheral blood.³

Cytokines

CRS can cause microvascular system damage, and a large number of cytokines such as IFN-γ and IL-6 are released, which can promote each other with the coagulation activation process, and finally form multi-organ failure. There are many cytokines associated with CRS, but the following are critical:

IL-2	Representing T cell activity, CAR-T releases IL-2 to maintain its own activity. High IL-2 levels indicate strong CAR-T activity.
IFN-γ	When CAR-T interacts with cancer cells, it releases IFN-γ to induce inflammation and activate monocytes and macrophages. The higher the IFN-γ level, the stronger the inflammatory response.
IL-6, IL-10	When monocytes and macrophages are activated, they release large amounts of cytokines, resulting in CRS. Studies have shown that severe CRS after CAR-T therapy is associated with high levels of IL-6 and IL-10.

Workflow

Fig.4 General flowchart for cytokine testing.⁴

Highlights

Extensive experience and expertise in in vivo research;
Keeping up with the times' technology platform and advanced instruments;
Reliable and complete data results and analysis reports;
Timely communication and global service;
Customized service.

Creative Biolabs is able to design rigorous and detailed preclinical in vivo research experiments with appropriate in vivo animal models or customized models tailored to your needs. If you have project needs in this field, please contact us now. Creative Biolabs is committed to accelerating your research and providing comprehensive and reliable protocols.

References

Xiao, X.; et al. "Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies." Journal of experimental & clinical cancer research. (2021) 40,1 367.
Bareham, B.; et al. "Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies." Cancer immunology, immunotherapy. 70,10 (2021): 2737-2750.
Morris, E.C.; et al. "Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy." Nat Rev Immunol. (2022) 22, 85–96.
Saxena, A.; et al. "Ultrasensitive quantification of cytokine proteins in single lymphocytes from human blood following ex-vivo stimulation." Frontiers in immunology. (2018) 9 2462.