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http://dx.doi.org/10.18419/opus-13097
Autor(en): | Aschmoneit, Nadine Steinlein, Sophia Kühl, Lennart Seifert, Oliver Kontermann, Roland E. |
Titel: | A scDb-based trivalent bispecific antibody for T-cell-mediated killing of HER3-expressing cancer cells |
Erscheinungsdatum: | 2021 |
Dokumentart: | Zeitschriftenartikel |
Seiten: | 12 |
Erschienen in: | Scientific reports 11 (2021), No. 13880 |
URI: | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-131164 http://elib.uni-stuttgart.de/handle/11682/13116 http://dx.doi.org/10.18419/opus-13097 |
ISSN: | 2045-2322 |
Zusammenfassung: | HER3 is a member of the EGF receptor family and elevated expression is associated with cancer progression and therapy resistance. HER3-specific T-cell engagers might be a suitable treatment option to circumvent the limited efficacy observed for HER3-blocking antibodies in clinical trials. In this study, we developed bispecific antibodies for T-cell retargeting to HER3-expressing tumor cells, utilizing either a single-chain diabody format (scDb) with one binding site for HER3 and one for CD3 on T-cells or a trivalent bispecific scDb-scFv fusion protein exhibiting an additional binding site for HER3. The scDb-scFv showed increased binding to HER3-expressing cancer cell lines compared to the scDb and consequently more effective T-cell activation and T-cell proliferation. Furthermore, the bivalent binding mode of the scDb-scFv for HER3 translated into more potent T-cell mediated cancer cell killing, and allowed to discriminate between moderate and low HER3-expressing target cells. Thus, our study demonstrated the applicability of HER3 for T-cell retargeting with bispecific antibodies, even at moderate expression levels, and the increased potency of an avidity-mediated specificity gain, potentially resulting in a wider safety window of bispecific T-cell engaging antibodies targeting HER3. |
Enthalten in den Sammlungen: | 04 Fakultät Energie-, Verfahrens- und Biotechnik |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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s41598-021-93351-0.pdf | 1,86 MB | Adobe PDF | Öffnen/Anzeigen |
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