In vivo generation of human CD 19‐ CAR T cells results in B‐cell depletion and signs of cytokine release syndrome
Open Access
- 17 September 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 10 (11), e9158
- https://doi.org/10.15252/emmm.201809158
Abstract
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 in vivo 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 in vivo reprogramming of human CD8+ CAR T cells active against CD19+ cells, yet with similar adverse effects currently notorious in the clinical practice.Funding Information
- Hessisches Ministerium für Wissenschaft und Kunst (llL5‐518/17.004)
- Deutsche Krebshilfe (70112587)
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