IBI302, a promising candidate for AMD treatment, targeting both the VEGF and complement system with high binding affinity in vitro and effective targeting of the ocular tissue in healthy rhesus monkeys

Ren, Xinyi; Li, Jia; Xu, Xianxing; Wang, Chunming; Cheng, Yiwei

doi:10.1016/j.exer.2016.02.004

Cited by 24 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, several neutralizing antibodies targeting VEGF, including bevacizumab, ranibizumab and aflibercept, are used for treating neovascular AMD and show good therapeutic effect clinically . Dual functional neutralizing antibody IBI302 targeting VEGF and complement system also showed promise as a candidate for AMD treatment . In our study, results demonstrated the protective role of SARI in laser‐induced CNV model in mice, evidenced by less leakage and severity of CNV in SARI WT mice.…”

Section: Discussionsupporting

confidence: 51%

SARI prevents ocular angiogenesis and inflammation in mice

Zhang

Dai

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

SARI (Suppressor of AP-1, regulated by IFN-β) is known to play an important role in some systemic disease processes such an inflammatory conditions and cancer. We hypothesize that SARI may also play a role in ocular diseases involving inflammation and neovascularization. To explore our hypothesis, further, we investigated an endotoxin-induced uveitis (EIU) and experimental argon laser-induced choroidal neovascularization (CNV) model in SARI wild-type (SARI WT ) and SARI-deficient (SARI −/− ) mice. Through imaging, morphological and immunohistochemical (IHC) studies, we found that SARI deficiency exacerbated the growth of CNV. More VEGF-positive cells were presented in the retina of SARI −/− mice with CNV. Compared to SARI WT mice, more inflammatory cells infiltrated the ocular anterior segment and posterior segments in SARI −/− mice with EIU. Collectively, the results point to a potential dual functional role of SARI in inflammatory ocular diseases, suggesting that SARI could be a potential therapy target for ocular inflammation and neovascularization. K E Y W O R D Sage-related macular degeneration, choroidal neovascularization, regulated by IFN-β, Suppressor of AP-1, Uveitis, vascular endothelial growth factor

show abstract

Section: Discussionsupporting

confidence: 51%

SARI prevents ocular angiogenesis and inflammation in mice

Zhang

Dai

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…The molecular size is approximately 156 kD, which is larger than eculizumab, suggesting the need to consider about the penetration problem. No concrete rate of penetration has been reported, but researchers are positive about its effective tissue targeting ability due to rather low systemic IBI302 level 82. Study about IBI302 is limited up till now, but we can infer that IBI302 is a potential candidate for AMD based on its favorite PK profiles and affinity ability revealed in existing information.…”

Section: Introductionmentioning

confidence: 94%

<p>Complement system and age-related macular degeneration: drugs and challenges</p>

Sun

2019

DDDT

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is directly attributable to vision loss, posing significant pressure on public health. AMD is recognized to be a multi-factorial disease and among them, complement system is under heated discussion in recent years. In this review, we start with an overview of complement pathways involved in AMD and their therapies correspondingly. Finally, we discuss the development of the therapeutics existed now. Also, we enclose a list of drugs undergoing clinical trials.

show abstract

“…A previous study has already confirmed that IBI302 can bind different VEGF isoforms including VEGF165, VEGF121, and PIGF and complement proteins C3b and C4b with high affinity [17]. IBI302 has showed an inhibitory effect on the VEGF165-induced cell proliferation of human primary umbilical vein endothelia and the activation of classical complement pathway and the alternative complement pathway in vitro [17]. Based on the critical role of complement in the inflammation of RPE cells, this study aimed to investigate the protective effect and its underlying mechanisms of IBI302 on human retinal pigment epithelial (hRPE) monolayer under the complement-activated oxidative stress.…”

Section: Introductionmentioning

confidence: 95%

“…It also has decay-accelerating activity against C3 convertases [16]. A previous study has already confirmed that IBI302 can bind different VEGF isoforms including VEGF165, VEGF121, and PIGF and complement proteins C3b and C4b with high affinity [17]. IBI302 has showed an inhibitory effect on the VEGF165-induced cell proliferation of human primary umbilical vein endothelia and the activation of classical complement pathway and the alternative complement pathway in vitro [17].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of a Bispecific Fc-Fusion Protein on the Barrier of Human Retinal Pigment Epithelial Cells

Wang

et al. 2021

Ophthalmic Res

Self Cite

View full text Add to dashboard Cite

To evaluate the protective effects of IBI302, a bi-specific Fc-fusion protein that theoretically can bind vascular endothelial growth factor (VEGF), complement C3b and C4b in the cultured human retinal pigment epithelial (hRPE) cells. Primary hRPE cells were isolated and cultured to monolayer barrier. hRPE monolayers were divided into control group, VEGF-Trap group, complement receptor 1 (CR1) group, and IBI302 group. Identification of hRPE cells, barrier function, inflammation factors and immune response products were tested by immunofluorescent staining, transepithelial resistance (TER) and ELISA. IBI302 treatment significantly improved TER of hRPE cells after complement-activated oxidative stress compared with control group, VEGF-Trap group, and CR1 group. The maximum effect of IBI302 on protecting hRPE cell viability was observed at the concentration of 1μg/ml. Elevated expression of VEGF, CCL2, C3a, C5a and MAC were inhibited by IBI302. IBI302 could protect the barrier function of hRPE cells. IBI302 might be a potentially effective drug for the RPE barrier-associated ocular diseases.

show abstract

IBI302, a promising candidate for AMD treatment, targeting both the VEGF and complement system with high binding affinity in vitro and effective targeting of the ocular tissue in healthy rhesus monkeys

Cited by 24 publications

References 19 publications

SARI prevents ocular angiogenesis and inflammation in mice

SARI prevents ocular angiogenesis and inflammation in mice

<p>Complement system and age-related macular degeneration: drugs and challenges</p>

Protective Effect of a Bispecific Fc-Fusion Protein on the Barrier of Human Retinal Pigment Epithelial Cells

Contact Info

Product

Resources

About