In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome
Paper cited by one technology page and one idea page, indexed on Europe PMC as PubMed record 30224381 and published in EMBO molecular medicine; the citing pages link this DOI, which is how the record was matched.
Overview
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.
Indexed on Europe PMC as PubMed record 30224381 (DOI 10.15252/emmm.201809158). Matched by DOI alone: one technology page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.
One technology page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
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