In Vitro CRS Models

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

Immunotherapeutic antibodies and cell therapies have proven to be highly effective cancer therapy. The therapy acts in part by stimulating and redirecting the immune system to attack cancer cells, and cytokines can be released during the process. As a consequence, cytokine release syndrome (CRS) is a common adverse effect which could be very severe in patients. The uses of in vitro CRS models improve the predictive capacity of in vitro cytokine release assays to reduce animal use and drug attrition. Creative Biolabs provides comprehensive in vitro CRS model development services or model products for global clients.

PBMCs

Peripheral blood mononuclear cells (PBMCs) are a heterogenous mix of white blood cells each having a round nucleus. The PBMC cellular model includes T and B cells (~80%), natural killer cells (~10%) and monocytes (~10%). Human/Non-human Primate (NHP) PBMCs can be used for a wide variety of immunology-based applications. In vitro immunoassays such as ELISPOT, mixed lymphocyte reactions, cytotoxicity assays, plaque assays are routinely performed using these cells. Besides, human PBMCs are routinely used in vitro to detect cytokine secretion as part of preclinical screens to delineate agonistic and antagonistic action of therapeutic drugs. For instance, this cell model could be used to determine the first-in-human dose.

CRS Assessment in In Vitro Model

Currently, there are four main methodologies for assessing CRS in vitro: whole blood (WB), PBMCs, high density PBMC, and blood outgrowth endothelial cell (BOEC) PBMC co-culture. Table 1 shows the assay systems, target cross linking and solution/phase of therapeutic presentation. When considering the format of the in vitro cytokine release assays (CRA), a definitive recommendation would not be made since it needs to be relevant to the understanding of mechanism of action (MOA) of the drug being tested. Assays using WB or PBMCs would be acceptable. Though WB assays are considered to be more physiological, PBMC assays may be more sensitive to reveal a cytokine signal.

Table 1 Table of assay format and the biological compound presentation.

*Asssay Format*	*Compound Solution/Phase*	*Physiological Compound Presentation*	*Target Cross-linking*	*FC-Binding*
PBMC	Liquid	Yes	No	No
PBMC	Dry and Wet	No	Yes	Yes
Whole Blood	Liquid	Yes	No	No
Whole Blood	Dry and Wet	No	Yes	Yes
High Density PBMC	Liquid	Yes	No	No
HUVEC PMBC Co-culture	Liquid	Yes	Yes	Yes
BOEC PBMC Co-culture	Liquid	Yes	Yes	Yes

Creative Biolabs offers PBMC, WB (liquid, dry immobilized, wet coating) and high density PBMC assay options as a standard and other in vitro services to complement nonclinical development plans. Our Customized in vitro CRS model development service is currently operating.

Features

High post-thaw viability PBMCs whenever your research demands.
PBMCs batch-tested negative for mycoplasma and bacteria by PCR
Serology screening
HLA typing available on request

Due to the fact of the cell model itself, it becomes increasingly clear that human/NHP WB or PBMC assays are not always predictive of in vivo CRS. In vivo CRS models are thus optional for you. Please feel free to contact us to find products and services to support your specific downstream applications.