Carl June, NIBR teams document CAR T resistance

A pair of Nature Medicine studies from CAR T pioneer Carl June and Novartis Institutes for BioMedical Research (NIBR) documented mechanisms that resulted in resistance to Kymriah tisagenlecleucel from Novartis AG (NYSE:NVS; SIX:NOVN) or its precursor CTL019 in patients with B cell acute lymphoblastic leukemia. The studies shine a light that could help optimize this promising therapy.

A University of Pennsylvania study from June and colleagues traced the origin of one patient's treatment failure with the university's CTL019 back to a single leukemic B cell that was unintentionally transduced with the CAR during manufacturing. As a result, the edited cancer cell and its progeny self-expressed anti-CD19 CARs, which masked the CD19 binding site and allowed them evade CAR T cell recognition. The CAR-edited cancer cells continued to expand despite salvage therapy and the patient relapsed and died...