TY  - JOUR
A1  - Pfeiffer, Anett
A1  - Thalheimer, Frederic Bastian
A1  - Hartmann, Sylvia
A1  - Frank, Annika
A1  - Bender, Ruben Raphael
A1  - Danisch, Simon
A1  - Costa, Caroline
A1  - Wels, Winfried
A1  - Modlich, Ute
A1  - Stripecke, Renata
A1  - Verhoeyen, Els
A1  - Buchholz, Christian
T1  - In vivo generation of human CD19‐CAR T cells results in B‐cell depletion and signs of cytokine release syndrome
T2  - EMBO molecular medicine
N2  - 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.
KW  - cytokine release syndrome
KW  - gene delivery
KW  - humanized mouse
KW  - T-cell targeting
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47384
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-473846
SN  - 1757-4684
SN  - 1715-4684
SN  - 1757-4676
N1  - © 2018 The Authors. Published under the terms of the CC BY 4.0 license
VL  - 10
IS  - e9158
SP  - 1
EP  - 11
PB  - Wiley-VCH ; EMBO Press
CY  - Weinheim ; Heidelberg
ER  -