Anett Pfeiffer, Frederic Bastian Thalheimer, Sylvia Hartmann, Annika Frank, Ruben Raphael Bender, Simon Danisch, Caroline Costa, Winfried Wels, Ute Modlich, Renata Stripecke, Els Verhoeyen, Christian Buchholz
- 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.
MetadatenAuthor: | Anett Pfeiffer, Frederic Bastian ThalheimerORCiDGND, Sylvia HartmannORCiDGND, Annika Frank, Ruben Raphael Bender, Simon Danisch, Caroline Costa, Winfried WelsORCiDGND, Ute ModlichORCiDGND, Renata Stripecke, Els Verhoeyen, Christian BuchholzORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-473846 |
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DOI: | https://doi.org/10.15252/emmm.201809158 |
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ISSN: | 1757-4684 |
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ISSN: | 1715-4684 |
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ISSN: | 1757-4676 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/30224381 |
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Parent Title (English): | EMBO molecular medicine |
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Publisher: | Wiley-VCH ; EMBO Press |
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Place of publication: | Weinheim ; Heidelberg |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2018 |
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Date of first Publication: | 2018/09/17 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2018/10/02 |
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Tag: | T-cell targeting; cytokine release syndrome; gene delivery; humanized mouse |
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Volume: | 10 |
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Issue: | e9158 |
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Page Number: | 11 |
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First Page: | 1 |
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Last Page: | 11 |
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Note: | © 2018 The Authors. Published under the terms of the CC BY 4.0 license |
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HeBIS-PPN: | 439188741 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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