دورية أكاديمية
Tumor Inhibitory Effect of IRCR201, a Novel Cross-Reactive c-Met Antibody Targeting the PSI Domain
| العنوان: | Tumor Inhibitory Effect of IRCR201, a Novel Cross-Reactive c-Met Antibody Targeting the PSI Domain |
|---|---|
| المؤلفون: | Hyunkyu Park, Donggeon Kim, Eunmi Kim, Jason K. Sa, Hee Won Lee, Suji Yu, Jiwon Oh, Seok-Hyung Kim, Yeup Yoon, Do-Hyun Nam |
| المصدر: | International Journal of Molecular Sciences, Vol 18, Iss 9, p 1968 (2017) |
| بيانات النشر: | MDPI AG, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | IRCR201, fully human antibody, cancer, c-Met, PSI domain, cross-reactivity, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy. Based on its protumorigenic potentials, we developed IRCR201, a potent antagonistic antibody targeting the plexin-semaphorin-integrin (PSI) domain of c-Met, using synthetic human antibody phage libraries. We characterized and evaluated the biochemical properties and tumor inhibitory effect of IRCR201 in vitro and in vivo. IRCR201 is a novel fully-human bivalent therapeutic antibody that exhibits cross-reactivity against both human and mouse c-Met proteins with high affinity and specificity. IRCR201 displayed low agonist activity and rapidly depleted total c-Met protein via the lysosomal degradation pathway, inhibiting c-Met-dependent downstream activation and attenuating cellular proliferation in various c-Met-expressing cancer cells. In vivo tumor xenograft models also demonstrated the superior tumor inhibitory responsiveness of IRCR201. Taken together, IRCR201 provides a promising therapeutic agent for c-Met-positive cancer patients through suppressing the c-Met signaling pathway and tumor growth. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 |
| Relation: | https://www.mdpi.com/1422-0067/18/9/1968; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms18091968 |
| URL الوصول: | https://doaj.org/article/e2a3da19278f4d3792315412c3096f49 |
| رقم الأكسشن: | edsdoj.2a3da19278f4d3792315412c3096f49 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 |
|---|---|
| DOI: | 10.3390/ijms18091968 |