Please use this identifier to cite or link to this item:
Volltext verfügbar? / Dokumentlieferung
doi:10.22028/D291-28872
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 http://dx.doi.org/10.22028/D291-28872 |
ISSN: | 0969-7128 1476-5462 |
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 |
Files for this record:
There are no files associated with this item.
Items in SciDok are protected by copyright, with all rights reserved, unless otherwise indicated.