Agne Taraseviciute, Victor Tkachev, Rafael Ponce, Cameron J Turtle, Jessica M Snyder, H Denny Liggitt, David Myerson, Luis Gonzalez-Cuyar, Audrey Baldessari, Chris English, Alison Yu, Hengqi Zheng, Scott N Furlan, Daniel J Hunt, Virginia Hoglund, Olivia Finney, Hannah Brakke, Bruce R Blazar, Carolina Berger, Stanley Riddell, Rebecca Gardner, Leslie S Kean, Michael C Jensen
Chimeric Antigen Receptor (CAR) T cell immunotherapy has revolutionised the treatment of refractory leukemias and lymphomas, but is associated with significant toxicities, namely cytokine release syndrome (CRS) and neurotoxicity. A major barrier to developing therapeutics to prevent CAR T cell-mediated neurotoxicity is the lack of clinically relevant models. Accordingly, we developed a rhesus macaque (RM) model of neurotoxicity via adoptive transfer of autologous CD20-specific CAR T cells. Following cyclophosphamide lymphodepletion, CD20 CAR T cells expand to 272-4450 cells/µl after 7-8 days and elicit CRS and neurotoxicity...
March 21, 2018: Cancer Discovery