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In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome.
- Source :
-
EMBO molecular medicine [EMBO Mol Med] 2018 Nov; Vol. 10 (11). - Publication Year :
- 2018
-
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 <superscript>+</superscript> cells. Administration into mice xenografted with Raji lymphoma cells and human peripheral blood mononuclear cells led to CAR expression solely in CD8 <superscript>+</superscript> T cells and efficacious elimination of CD19 <superscript>+</superscript> B cells. Further, upon injection of CD8-LV into mice transplanted with human CD34 <superscript>+</superscript> cells, induction of CAR T cells and CD19 <superscript>+</superscript> 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 <superscript>+</superscript> CAR T cells active against CD19 <superscript>+</superscript> cells, yet with similar adverse effects currently notorious in the clinical practice.<br /> (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)
Details
- Language :
- English
- ISSN :
- 1757-4684
- Volume :
- 10
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- EMBO molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30224381
- Full Text :
- https://doi.org/10.15252/emmm.201809158