Few assays are currently available that identify patients who are at risk of developing severe cytokine release syndrome (CRS) and neurotoxicity following adoptive T cell immunotherapy. CRS and neurotoxicity usually occur within the first 1-2 weeks after in vivo CAR-T cell activation and proliferation, complicating wide adoption of adoptive cell therapies given the specialized care. Although CRS and neurotoxicity can be reversed, severe cases can result in intensive care admission and in some cases, be fatal. Dr. Turtle and his colleagues have identified biomarker signatures in patient samples after adoptive T cell therapy associated with endothelial activation, initiation of intravascular coagulation and blood-brain barrier leak. The Turtle Lab has identified a biomarker panel to detect and identify these biomarkers in patient serum before lymphodepletion, chemotherapy, or adoptive cell therapy infusion. These biomarkers will help in risk assessment of patients receiving adoptive T cell therapy, and to inform dosing and other pre-emptive treatments in order to minimize and prevent severe and potentially life-threatening CRS and neurotoxicity.
Method used for evaluating risk of developing severe CRS or neurotoxicity following adoptive T cell therapy
Useful for early intervention, modification of therapeutic regimes or both to minimize patient risk Applicable before or after conditioning, cellular immunotherapy or both
Allows for either pre-emptive intervention or exclusion from the therapy to minimize the risks of poor outcomes
Measurement of biomarkers prior to CAR T cell infusion can determine dosing of the active agent to avoid CRS
The Global CAR T Cell Therapy market is predicted to be worth USD 8.92 billion by 2026, with an expanding compound annual growth rate (CAGR) of 34.5% from 2020 to 2026. Continuous research and development, along with ongoing regulatory approvals, and better cancer awareness centers are all predicted to drive this market forward. CRS remains problematic with ongoing trials and precludes its widespread adoption at community cancer centers given specialized nursing and the high level of monitoring required.
Cameron Turtle, M.B.B.S., Ph.D., F.R.A.C.P., F.R.C.P.A., Clinical Research Division