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Updated: Sep 2, 2025

Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
Adaptable Leukemia Cells Resisting CAR T-cell Attack via B-cell Activation
Ziran Zhao1, Jan Joseph Melenhorst1
1Cell Therapy & Immuno-Engineering Program, Center for ImmunoTherapy & Precision Immuno-Oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Abstract:
Chimeric antigen receptor (CAR) T-cell therapy has achieved remarkable milestones in the treatment of B-cell malignancies. However, cancer cells frequently survive CAR T-cell killing in a large cohort of patients. Relapse oftentimes is associated with antigen loss. In this issue, Im and colleagues report a new mechanism of leukemic-cell resistance to anti-CD19 CAR T cells: Leukemic cells can enable a B-cell activation and germinal center reaction signature, which causes CD19 transcriptional downregulation and survival from CAR exposure. See related article by Im et al., p. 1055 (5).
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