generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome.

Chimeric antigen receptor (CAR) T cells brought substantial benefit to patients with B-cell malignancies. Notwithstanding, CAR T-cell manufacturing requires complex procedures impeding the broad supply chain. Here, we provide evidence that human CD19-CAR T cells can be generated directly using the lentiviral vector CD8-LV specifically targeting human CD8 cells. Administration into mice xenografted with Raji lymphoma cells and human peripheral blood mononuclear cells led to CAR expression solely in CD8 T cells and efficacious elimination of CD19 B cells. Further, upon injection of CD8-LV into mice transplanted with human CD34 cells, induction of CAR T cells and CD19 B-cell depletion was observed in 7 out of 10 treated animals. Notably, three mice showed elevated levels of human cytokines in plasma. Tissue-invading CAR T cells and complete elimination of the B-lymphocyte-rich zones in spleen were indicative of a cytokine release syndrome. Our data demonstrate the feasibility of reprogramming of human CD8 CAR T cells active against CD19 cells, yet with similar adverse effects currently notorious in the clinical practice.