Please use this identifier to cite or link to this item: doi:10.22028/D291-28872
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Title: Primary T cells for mRNA-mediated immunotoxin delivery
Author(s): Eggers, Rick
Philippi, Anja
Altmeyer, Matthias
Breinig, Frank
Schmitt, Manfred J.
Language: English
Title: Gene therapy
Volume: 25
Issue: 1
Startpage: 47
Endpage: 53
Publisher/Platform: Nature Publishing Group
Year of Publication: 2017
Publikation type: Journal Article
Abstract: Immune cells become increasingly attractive as delivery system for immunotoxins in cancer therapy to reduce the intrinsic toxicity and severe side effects of chimeric protein toxins. In this study, we investigated the potential of human primary T cells to deliver a secreted immunotoxin through transient messenger RNA (mRNA) transfection. The chimeric protein toxin was directed toward the neovasculature of cancer cells by fusing a truncated version of Pseudomonas exotoxin A (PE38) to human vascular endothelial growth factor (VEGF) and to the single chain variable fragment (scFv) of anti-Her2/neu. Protocols for the transient transfection of human embryonic kidney cells (HEK293) as well as activated primary human T cells were established. Transient transfection with mRNA coding for the immunotoxins e23-PE38, VEGF-PE38 and its attenuated variant VEGF-PE38D yielded efficient expression and secretion. Mass spectrometry analysis endorsed that a fraction of VEGF-PE38D was properly translocated into the endoplasmic reticulum. Furthermore, cytotoxic activity of immunotoxin secreting T cells toward cancer cells was confirmed in co-culture with ovarian adenocarcinoma cells in the presence of a bispecific antibody (bsAb), highlighting the potential of primary T cells for mRNA-mediated immunotoxin delivery.
DOI of the first publication: 10.1038/gt.2017.87
Link to this record: hdl:20.500.11880/27759
ISSN: 0969-7128
Date of registration: 13-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Manfred Schmitt
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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