N. Steere, P. Younge, R. Weller Roska, M. Davila*, M. Anderson
The ability of the human immune system to discern and eliminate malignancies is well established and has recently become an important focus in oncology research. Current cancer immunotherapy seeks to direct and bolster an individual’s anti-tumor immune response. One of the most promising approaches being studied is chimeric antigen receptor T cell (CAR T) therapy. Chimeric antigen receptors, when expressed in an individual’s T cells, facilitate both binding to specific antigen expressing tumor cells, and subsequent T cell activation (1). Monitoring and characterizing the response to CAR T therapy has been an ongoing challenge for researchers. Biomarkers associated with T cell activation and cytokine release syndrome (CRS) are of particular interest (2). Fast and accurate quantitation of such markers allows for the detailed analysis of an individual’s response to T-cell infusion and the cytokines associated with the CRS toxicity.
In order to characterize the dynamic molecular response to CAR T cell infusion, three CAR T therapy donor sample sets (human serum; 10 time points including pre and post-treatment for each donor), were assayed using the Ella™ multi-analyte immunoassay platform. Multiple markers for CRS and T cell activity were profiled including IFN-gamma, IL-6, TNF-alpha, Granzyme A and Granzyme B. Based on the literature, we expected to observe an increase in established CRS and T cell marker levels soon after the T cell infusion. Our data indicated that each donor presented a unique response profile. Elevated levels of many markers were observed, with the degree of elevation and response time relative to T cell infusion varying between sample sets. For instance, one donor showed little observable response until IL-6 increased drastically four days after infusion. By contrast, a second donor responded with increasing levels of IFN-gamma, IL-10, IL-6, and Granzyme B within 48 hours of infusion. These results highlight the complexity of the immune response to CAR-T cell infusion over time, and the ability to observe that response across a range of markers.
- Sadelain, M et al. (2013) Cancer Discovery. 3: 388
- Lacery, S.F. and Kalos M. (2013) Cytotherapy. 15: 632