T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). CAR-T cells have demonstrated clinical efficacy in hematologic malignancies and targeting solid tumors. However, CAR-T therapy also can elicit cytokine release syndrome (CRS) cytotoxicity. This unwanted release of cytokines has also been seen following the infusion of therapeutic monoclonal antibodies (mAbs), systemic interleukin-2 (IL-2), and the bispecific CD19-CD3 T-cell engaging antibody blinatumomab.
The hallmark of CRS is immune activation resulting in elevation of inflammatory cytokines. To different extents, change of cytokines/chemokine levels for GM-CSF, Granzyme B, IFN-γ, MIP-1α, TNF-α, IL-2, IL, 4, IL-6, IL-8, IL-10, IL-13, IL-22, and IL-17A have been shown following CAR T-cell infusion.
At BioAgilytix, we have been using the three 10-plex cytokine panels from Meso Scale Discovery (MSD) to support various CAR-T programs and enable our clients to follow various cytokine levels, including monitoring the level of CRS during their CAR-T therapy. The three panels below provide a list of the biomarkers that have gone through full bioanalytical validations at BioAgilytix in support of clinical trials.
- IL-12/23 p40
- IL-12 p70
- IL-8 (High Abundance)
Selection of pre-validated panel of inflammatory cytokines is a cost-effective way to meet most bioanalytical needs to assess immune activation. We acknowledge clinical teams have and may require additional cytokines be measured outside of the panels, and stand ready to bring to application-specific standalone methods to cover those analytes.
If you are working on a CAR-T program and/or other therapies in which CRS may be of concern, and need accurate measurement of series of cytokines, please contact our scientific team today and we will be happy to discuss your specific project needs.