مورد إلكتروني
Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action
| العنوان: | Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action |
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| المؤلفون: | Kast, Florian; https://orcid.org/0000-0001-5586-8382, Schwill, Martin; https://orcid.org/0000-0002-2798-5490, Stüber, Jakob C; https://orcid.org/0000-0002-3406-0664, Pfundstein, Svende, Nagy-Davidescu, Gabriela, Rodríguez, Josep M Monné, Seehusen, Frauke, Richter, Christian P, Honegger, Annemarie; https://orcid.org/0000-0002-3378-3967, Hartmann, Karen Patricia, Weber, Thomas G, Kroener, Felix, Ernst, Patrick; https://orcid.org/0000-0001-6037-1856, Piehler, Jacob, Plückthun, Andreas; https://orcid.org/0000-0003-4191-5306 |
| المصدر: | Kast, Florian; Schwill, Martin; Stüber, Jakob C; Pfundstein, Svende; Nagy-Davidescu, Gabriela; Rodríguez, Josep M Monné; Seehusen, Frauke; Richter, Christian P; Honegger, Annemarie; Hartmann, Karen Patricia; Weber, Thomas G; Kroener, Felix; Ernst, Patrick; Piehler, Jacob; Plückthun, Andreas (2021). Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action. Nature Communications, 12:3790. |
| بيانات النشر: | Nature Publishing Group 2021-06-18 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | The receptor tyrosine kinase HER2 acts as oncogenic driver in numerous cancers. Usually, the gene is amplified, resulting in receptor overexpression, massively increased signaling and unchecked proliferation. However, tumors become frequently addicted to oncogenes and hence are druggable by targeted interventions. Here, we design an anti-HER2 biparatopic and tetravalent IgG fusion with a multimodal mechanism of action. The molecule first induces HER2 clustering into inactive complexes, evidenced by reduced mobility of surface HER2. However, in contrast to our earlier binders based on DARPins, clusters of HER2 are thereafter robustly internalized and quantitatively degraded. This multimodal mechanism of action is found only in few of the tetravalent constructs investigated, which must target specific epitopes on HER2 in a defined geometric arrangement. The inhibitory effect of our antibody as single agent surpasses the combination of trastuzumab and pertuzumab as well as its parental mAbs in vitro and it is effective in a xenograft model. |
| مصطلحات الفهرس: | Department of Biochemistry, Institute of Veterinary Pathology, 570 Life sciences; biology, 610 Medicine & health, Journal Article, PeerReviewed, info:eu-repo/semantics/article, info:eu-repo/semantics/publishedVersion |
| URL: | 10.1038/s41467-021-23948-6 |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess Creative Commons: Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf info:doi/10.5167/uzh-210200 English |
| أرقام أخرى: | CHUZH oai:www.zora.uzh.ch:210200 https://www.zora.uzh.ch/id/eprint/210200/1/Kast_et_al_2021.pdf info:doi/10.5167/uzh-210200 info:doi/10.1038/s41467-021-23948-6 info:pmid/34145240 urn:issn:2041-1723 1443041389 |
| المصدر المساهم: | HAUPTBIBLIOTHEK UNIV OF ZURICH From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1443041389 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |