Please use this identifier to cite or link to this item: http://dx.doi.org/10.18419/opus-14887
Full metadata record
DC FieldValueLanguage
dc.contributor.authorDilchert, Janine-
dc.contributor.authorHofmann, Martin-
dc.contributor.authorUnverdorben, Felix-
dc.contributor.authorKontermann, Roland-
dc.contributor.authorBunk, Sebastian-
dc.date.accessioned2024-08-28T09:26:18Z-
dc.date.available2024-08-28T09:26:18Z-
dc.date.issued2022de
dc.identifier.issn2073-4468-
dc.identifier.other1901908569-
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-149068de
dc.identifier.urihttp://elib.uni-stuttgart.de/handle/11682/14906-
dc.identifier.urihttp://dx.doi.org/10.18419/opus-14887-
dc.description.abstractBispecific T cell receptor (TCR)-based molecules capable of redirecting and activating T cells towards tumor cells represent a novel and promising class of biotherapeutics for the treatment of cancer. Usage of TCRs allows for targeting of intracellularly expressed and highly selective cancer antigens, but also requires a complex maturation process to increase the naturally low affinity and stability of TCRs. Even though TCR domains can be matured via phage and yeast display, these techniques share the disadvantages of non-human glycosylation patterns and the need for a later reformatting into the final bispecific format. Here, we describe the development and application of a Chinese Hamster Ovary (CHO) display for affinity engineering of TCRs in the context of the final bispecific TCR format. The recombinase-mediated cassette exchange (RCME)-based system allows for stable, single-copy integration of bispecific TCR molecules with high efficiency into a defined genetic locus of CHO cells. We used the system to isolate affinity-increased variants of bispecific T cell engaging receptor (TCER) molecules from a library encoding different CDR variants of a model TCR targeting preferentially expressed antigen in melanoma (PRAME). When expressed as a soluble protein, the selected TCER molecules exhibited strong reactivity against PRAME-positive tumor cells associated with a pronounced cytokine release from activated T cells. The obtained data support the usage of the CHO display-based maturation system for TCR affinity maturation in the context of the final bispecific TCER format.en
dc.description.sponsorshipImmatics Biotechnologies GmbHde
dc.language.isoende
dc.relation.uridoi:10.3390/antib11020034de
dc.rightsinfo:eu-repo/semantics/openAccessde
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/de
dc.subject.ddc570de
dc.titleMammalian display platform for the maturation of bispecific TCR-based moleculesen
dc.typearticlede
dc.date.updated2023-11-14T02:07:06Z-
ubs.fakultaetEnergie-, Verfahrens- und Biotechnikde
ubs.fakultaetFakultätsübergreifend / Sonstige Einrichtungde
ubs.institutInstitut für Zellbiologie und Immunologiede
ubs.institutFakultätsübergreifend / Sonstige Einrichtungde
ubs.publikation.seiten19de
ubs.publikation.sourceAntibodies 11 (2022), No. 34de
ubs.publikation.typZeitschriftenartikelde
Appears in Collections:04 Fakultät Energie-, Verfahrens- und Biotechnik

Files in This Item:
File Description SizeFormat 
antibodies-11-00034.pdf3,04 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons