A Review of Aflibercept Treatment for Macular Disease

Anguita, Rodrigo; Tasiopoulou, Anastasia; Shahid, Syed; Roth, Jeffrey C.; Sim, Sing Yue; Patel, Praveen J

doi:10.1007/s40123-021-00354-1

Cited by 17 publications

(12 citation statements)

References 65 publications

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“…We next tested whether the EMAD13 module, in addition to loading vaccine antigens, could also load therapeutically-important of proteins into the exosome membrane. We therefore created Tet-on 293 cells designed to express EMAD13-tagged forms of the VEGF inhibitor aflibercept( 43, 44 ), the Fabry disease protein alpha galactosidase A( 45, 46 ), and the heavy chain (HC) of the anti-HER2 monoclonal antibody trastuzumab( 47, 48 ) (co-expressed with the trastuzumab light chain (LC)) (sequences provided in table S2 ). These cell lines were grown in doxycycline-containing medium for three days, after which cell and exosome fractions were collected, and examined by immunoblot.…”

Section: Resultsmentioning

confidence: 99%

Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein

Guo,

Sachithanandham,

Zhong

et al. 2024

Preprint

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As the only bionormal nanovesicle, exosomes have high potential as a nanovesicle for delivering vaccines and therapeutics. We show here that the loading of type-1 membrane proteins into the exosome membrane is induced by exosome membrane anchor domains, EMADs, that maximize protein delivery to the plasma membrane, minimize protein sorting to other compartments, and direct proteins into exosome membranes. Using SARS-CoV-2 spike as an example and EMAD13 as our most effective exosome membrane anchor, we show that cells expressing a spike-EMAD13 fusion protein produced exosomes that carry dense arrays of spike trimers on 50% of all exosomes. Moreover, we find that immunization with spike-EMAD13 exosomes induced strong neutralizing antibody responses and protected hamsters against SARS-CoV-2 disease at doses of just 0.5-5 ng of spike protein, without adjuvant, demonstrating that antigen-display exosomes are particularly immunogenic, with important implications for both structural and expression-dependent vaccines.

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Section: Resultsmentioning

confidence: 99%

Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein

Guo,

Sachithanandham,

Zhong

et al. 2024

Preprint

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“…Regarding this overexpression of inflammatory cytokines, the use of monoclonal antibodies against VEGF has been established as a valuable alternative to more traditional treatments (surgery and laser photocoagulation) [ 11 , 13 ]. The most used anti-VEGF antibodies are ranibizumab, bevacizumab, aflibercept, and faricimab [ 14 , 15 , 16 ]. However, the therapeutic use of these antibodies presents some drawbacks such as their high cost, short half-life, the occurrence of side effects (e.g., inflammation, retinal detachment, or increased ocular pressure), or the need for repeated intravitreal injections to administrate the antibodies.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition

et al. 2023

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AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences that can adopt a G-quadruplex (G4) structure and target nucleolin (NCL), a protein that acts as a co-receptor for several growth factors. Hence, this study aimed to characterize the AT11-L0 G4 structure and its interaction with several ligands for NCL targeting and to evaluate their capacity to inhibit angiogenesis using an in vitro model. The AT11-L0 aptamer was then used to functionalize drug-associated liposomes to increase the bioavailability of the aptamer-based drug in the formulation. Biophysical studies, such as nuclear magnetic resonance, circular dichroism, and fluorescence titrations, were performed to characterize the liposomes functionalized with the AT11-L0 aptamer. Finally, these liposome formulations with the encapsulated drugs were tested on the human umbilical vein endothelial cell (HUVEC) model to assess their antiangiogenic capacity. The results showed that the AT11-L0 aptamer–ligand complexes are highly stable, presenting melting temperatures from 45 °C to 60 °C, allowing for efficient targeting of NCL with a KD in the order of nM. The aptamer-functionalized liposomes loaded with ligands C8 and dexamethasone did not show cytotoxic effects in HUVEC cells compared with the free ligands and AT11-L0, as assessed by cell viability assays. AT11-L0 aptamer-functionalized liposomes encapsulating C8 and dexamethasone did not present a significant reduction in the angiogenic process when compared with the free ligands. In addition, AT11-L0 did not show anti-angiogenic effects at the concentrations tested. However, C8 shows potential as an angiogenesis inhibitor, which should be further developed and optimized in future experiments.

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“…35,36 Neovascular AMD is characterized by abnormal growth of choroidal blood vessels through Bruch's membrane, generally confined below the retinal pigment epithelium (RPE) and/or retina, although it can also penetrate beyond the subretinal space and within the retina, progressing to retinal angiomatous proliferation. 37 These "new" vessels are leaky and proliferative and may eventually lead to fibrosis and scarring, contributing to significant vision loss. [35][36][37][38]…”

mentioning

confidence: 99%

“…37 These "new" vessels are leaky and proliferative and may eventually lead to fibrosis and scarring, contributing to significant vision loss. [35][36][37][38]…”

mentioning

confidence: 99%

Progress and Challenges of Anti-VEGF Agents and Their Sustained-Release Strategies for Retinal Angiogenesis

Xu¹,

Fan²,

Fan³

et al. 2022

DDDT

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Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.

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A Review of Aflibercept Treatment for Macular Disease

Cited by 17 publications

References 65 publications

Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein

Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein

Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition

Progress and Challenges of Anti-VEGF Agents and Their Sustained-Release Strategies for Retinal Angiogenesis

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