Bellicum announces first reported use of CaspaCIDe safety switch to mitigate CAR-T cell toxicity.

Bellicum Pharmaceuticals, Inc., a leader in developing novel, controllable cellular immunotherapies for cancers, announced the publication of a case report using the company’s CaspaCIDe (inducible caspase-9, or iC9) safety switch. The letter to the editor titled “Utility of Safety Switch to Abrogate CD 19 CAR T Cell-Associated Neurotoxicity” appeared as an ahead-of-print publication in the digital edition of Blood, a journal published by The American Society of Hematology. The publication detailed a case report from an investigator-sponsored trial (IST) at the University of North Carolina Lineberger Comprehensive Cancer Center, where a Phase 1/II trial is ongoing to test the safety and efficacy of autologous T lymphocytes genetically modified to express a CD19 chimeric antigen receptor (CAR) and iC9. A patient in the dose expansion cohort of this trial experienced a high grade neurologic adverse event with persistence of grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS) for 72 hours despite standard care, and rimiducid was subsequently given per protocol to activate iC9. Within twelve hours of rimiducid administration, ICANS grade improved from 3 to 1 and was fully resolved after four days. This publication marked the first reported clinical use of the iC9 safety switch to mitigate a severe CAR-T-mediated adverse event refractory to standard of care treatment. “Given the risks of ICANS and other CAR-T cell-mediated adverse events, the inclusion of the iC9 switch has the potential to dramatically improve the safety of cellular immunotherapies,” said Matthew Foster, M.D., University of North Carolina Lineberger Comprehensive Cancer Center. “We are also encouraged by the anti-leukemic response we observed in this patient even with the use of the iC9 switch.” See-_" Utility of Safety Switch to Abrogate CD19.CAR T Cell-Associated Neurotoxicity"- Matthew C Foster , Barbara Savoldo , Winnie Lau , Clio A Rubinos , Natalie Grover , Paul M Armistead , James M. Coghill , Robert S Hagan , J. Kaitlin Morrison , Catherine Cheng , Spencer Laing , Anastasia Ivanova , John West , Aaron Foster , Jonathan Serody , Gianpietro Dotti. Blood blood.2021010784. https://doi.org/10.1182/blood.2021010784.