Wang X, Urak R, Walter M, et al. Large-Scale Manufacturing and Characterization of CMV-CD19CAR T Cells. Journal for ImmunoTherapy of Cancer. 2022; (doi: 10.1136/jitc-2021-003461).
Researchers have developed and validated a large-scale clinical platform for generating CD19-targeted chimeric antigen receptor T cells (CAR-T) that are specific to cytomegalovirus (CMV). The process isolates and stimulates peripheral blood mononuclear cells harvested from healthy CMV-seropositive donors, and then enriches them before CD19CAR transduction. The resulting CMV-CD19CAR T cells express memory markers but have low expression of exhaustion markers. They react to CD19 and CMVpp65 stimulation with rapid proliferation and display antigen-specific effector functions against tumors that express CD19 and CMVpp65 antigen. Earlier work with a mouse model demonstrated that using CMV vaccination to expand these cells in vivo translated to better tumor control. The team is preparing to move forward with a clinical study that will use CMV-CD19CAR T cells in patients with intermediate/high-grade B cell non-Hodgkin's lymphoma immediately after autologous hematopoietic cell transplantation, followed by CMV vaccination.