Krug, Christian, Wiesinger, Manuel, Abken, Hinrich, Schuler-Thurner, Beatrice, Schuler, Gerold, Dorrie, Jan ORCID: 0000-0002-3478-0741 and Schaft, Niels ORCID: 0000-0001-8236-9298 (2014). A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA encoding a tumor-specific chimeric antigen receptor. Cancer Immunol. Immunother., 63 (10). S. 999 - 1009. NEW YORK: SPRINGER. ISSN 1432-0851

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Abstract

Chimeric antigen receptors (CARs), which combine an antibody-derived binding domain (single chain fragment variable) with T-cell-activating signaling domains, have become a promising tool in the adoptive cellular therapy of cancer. Retro- and lenti-viral transductions are currently the standard methods to equip T cells with a CAR; permanent CAR expression, however, harbors several risks like uncontrolled auto-reactivity. Modification of T cells by electroporation with CAR-encoding RNA to achieve transient expression likely circumvents these difficulties. We here present a GMP-compliant protocol to activate and expand T cells for clinical application. The protocol is optimized in particular to produce CAR-modified T cells in clinically sufficient numbers under full GMP-compliance from late-stage cancer patients. This protocol allows the generation of 6.7 x 10(8) CAR-expressing T cells from one patient leukapheresis. The CAR-engineered T cells produced pro-inflammatory cytokines after stimulation with antigen-bearing tumor cells and lysed tumor cells in an antigen-specific manner. This functional capacity was maintained after cryopreservation. Taken together, we provide a clinically applicable protocol to transiently engineer sufficient numbers of antigen-specific patient T cells for use in adoptive cell therapy of cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Krug, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesinger, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abken, HinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuler-Thurner, BeatriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuler, GeroldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dorrie, JanUNSPECIFIEDorcid.org/0000-0002-3478-0741UNSPECIFIED
Schaft, NielsUNSPECIFIEDorcid.org/0000-0001-8236-9298UNSPECIFIED
URN: urn:nbn:de:hbz:38-427586
DOI: 10.1007/s00262-014-1572-5
Journal or Publication Title: Cancer Immunol. Immunother.
Volume: 63
Number: 10
Page Range: S. 999 - 1009
Date: 2014
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-0851
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ADOPTIVE IMMUNOTHERAPY; RECOMBINANT IMMUNORECEPTORS; ACTIVATION; ELUTRIATION; MELANOMA; THERAPYMultiple languages
Oncology; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42758

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