Tumor Inhibitory Effect of IRCR201, a Novel Cross-Reactive c-Met Antibody Targeting the PSI Domainopen access
- Authors
- Park, H[Park, Hyunkyu]; Kim, D[Kim, Donggeon]; Kim, E[Kim, Eunmi]; Sa, JK[Sa, Jason K.]; Lee, HW[Lee, Hee Won]; Yu, S[Yu, Suji]; Oh, J[Oh, Jiwon]; Kim, SH[Kim, Seok-Hyung]; Yoon, Y[Yoon, Yeup]; Nam, DH[Nam, Do-Hyun]
- Issue Date
- Sep-2017
- Publisher
- MDPI AG
- Keywords
- IRCR201; fully human antibody; cancer; c-Met; PSI domain; cross-reactivity
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.18, no.9
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 18
- Number
- 9
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/27495
- DOI
- 10.3390/ijms18091968
- ISSN
- 1422-0067
- Abstract
- 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.
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Collections - Samsung Advanced Institute for Health Sciences and Technology, SKKU > ETC > 1. Journal Articles
- Medicine > Department of Medicine > 1. Journal Articles
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