Ranibizumab and aflibercept for the treatment of wet age-related macular degeneration

Yazdi, Mohammad Hossein; Faramarzi, Mohammad Ali; Nikfar, Shekoufeh; Falavarjani, Khalil Ghasemi; Abdollahi, Mohammad

doi:10.1517/14712598.2015.1057565

Cited by 23 publications

(13 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 52 Recently, a new monoclonal antibody (ranibizumab, Novartis) drug was approved by FDA in 2015 and is now in clinical use to compete with Macugen. 53 Since naked nucleic acid drugs are easily degraded by nuclease, unstable in blood and hard to pass the cell membrane, the administration method of the 6 FDA-approved oligo drugs so far were either vitreous injection (Fomivirsen and Macugen), intrathecal injection (Nusinersen), targeting blood component (Defibrotide) to avoid drug delivery process or apply large dose to fulfil therapeutic effect (Mipomersen and Eteplirsen) accompanied by side effect such as liver toxicity. Although aptamers showed advantages over antibody with lower toxicity, smaller size, and less immune reaction, chemical modifications to increase their affinity, specificity, and enzymatic stability must still be explored, together with effective delivery technologies.…”

Section: Discussionmentioning

confidence: 99%

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Fan

Sun

et al. 2017

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

In this study, chemical modification of 2′-deoxyinosine (2′-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement. They stabilized the G-quadruplex, remained highly resistant to serum degradation and specificity for nucleolin, further inhibited tumor cell growth, exhibited a stronger ability to influence the different phases of the tumor cell cycle, induced S-phase arrest, promoted the inhibition of DNA replication, and suppressed the unwound function of a large T antigen as powerful as AS1411. The microarray analysis and TaqMan PCR results showed that FCL-II can upregulate the expression of four breast-cancer-related, lowly expressed miRNAs and downregulate the expression of three breast-cancer-related, highly expressed miRNAs (>2.5-fold). FCL-II resulted in enhanced treatment effects greater than AS1411 in animal experiments (p < 0.01). The computational results further proved that FCL-II exhibits more structural advantages than AS1411 for binding to the target protein nucleolin, indicating its great potential in antitumor therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Fan

Sun

et al. 2017

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“…For these phenomena, researchers have offered various descriptions and explanations about the loss of the drug’s effectiveness, such as “incomplete response”, 29 “poor response”, 30 “nonresponse”, 30 , 31 “unresponsive”, 32 “tolerance”, 33 – 35 “tachyphylaxis”, 34 – 40 “treatment resistant”, 41 – 43 “resistance to anti-VEGF”, 44 “refractory to anti-VEGF”, 45 and “resistance to anti-VEGF treatment”. 46 When describing and classifying patients with persistent fluid or recurrent exudation, researchers frequently use the terms “refractory neovascular AMD”, 47 – 50 “recalcitrant neovascular AMD”, 51 – 54 “recurrent neovascular AMD”, 44 , 47 , 55 – 57 and “treatment-resistant neovascular AMD”.…”

Section: Introductionmentioning

confidence: 99%

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

Yang¹,

Zhao²,

Sun³

2016

DDDT

188

113

View full text Add to dashboard Cite

As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.

show abstract

“…8, 9, 10, 11, 12, 13 Bevacizumab, a humanized antibody to VEGF, ranibizumab, a fragment antigen-binding (Fab) fragment of bevacizumab and aflibercept (VEGF-Trap) are the leading biological drugs targeting VEGF, and are used in clinics to suppress VEGF-dependent abnormal angiogenesis in the progression of cancers and wet AMD. 14, 15, 16, 17 However, resistance to these drugs remains a major hurdle in improving clinical outcomes. 18, 19 To this end, we focused on identifying a novel therapeutic target and elucidating its functional roles and mechanisms of action in angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis

Kim

Park

et al. 2017

Exp Mol Med

View full text Add to dashboard Cite

Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation. We demonstrated that a monoclonal antibody specific to VCAM-1-D6 suppressed TNFα-induced endothelial cell migration and tube formation and TNFα-induced vessel sprouting in rat aortas. We also found that the antibody insignificantly affected endothelial cell viability, morphology and activation. Finally, the antibody specifically blocked VCAM-1-mediated cell–cell contacts by directly inhibiting VCAM-1-D6-mediated interaction between VCAM-1 molecules. These findings suggest that VCAM-1-D6 may be a potential novel therapeutic target in TNFα-induced angiogenesis and that antibody-based modulation of VCAM-1-D6 may be an effective strategy to suppress TNFα-induced angiogenesis.

show abstract

Ranibizumab and aflibercept for the treatment of wet age-related macular degeneration

Cited by 23 publications

References 50 publications

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis

Contact Info

Product

Resources

About