Pharmacologic and Pharmacokinetic Assessment of Anti-TGFβ2 Aptamers in Rabbit Plasma and Aqueous Humor

McCauley, Thomas G.; Kurz, Jeffrey C.; Merlino, Patricia G.; Lewis, Scott D.; Gilbert, Madaline; Epstein, David; Marsh, H. Nicholas

doi:10.1007/s11095-005-9305-2

Cited by 34 publications

(14 citation statements)

References 15 publications

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“…Binding reactions were prepared with radiolabeled AX102 (V10 pmol/L) and increasing concentrations (0.001-60 nmol/L) of recombinant PDGF or VEGF in PBS (Invitrogen) containing 0.1 mg/mL bovine serum albumin (EMD Biosciences) and 0.01 mg/mL tRNA (Sigma). Nitrocellulose filtration and analysis was done essentially as described (25) to obtain estimates of the dissociation constant (K D ). The pharmacokinetic analysis and pharmacodynamic assay were done as described in Supplementary Methods.…”

Section: Methodsmentioning

confidence: 99%

Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells after Inhibition of Platelet-Derived Growth Factor B by Selective Aptamer AX102

et al. 2007

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Inhibition of platelet derived growth factor (PDGF) can increase the efficacy of other cancer therapeutics, but the cellular mechanism is incompletely understood. We examined the cellular effects on tumor vasculature of a novel DNA oligonucleotide aptamer (AX102) that selectively binds PDGF-B. Treatment with AX102 led to progressive reduction of pericytes, identified by PDGF receptor B, NG2, desmin, or A-smooth muscle actin immunoreactivity, in Lewis lung carcinomas. The decrease ranged from 35% at 2 days, 63% at 7 days, to 85% at 28 days. Most tumor vessels that lacked pericytes at 7 days subsequently regressed. Overall tumor vascularity decreased 79% over 28 days, without a corresponding decrease in tumor size. Regression of pericytes and endothelial cells led to empty basement membrane sleeves, which were visible at 7 days, but only 54% remained at 28 days. PDGF-B inhibition had a less pronounced effect on pancreatic islet tumors in RIP-Tag2 transgenic mice, where pericytes decreased 47%, vascularity decreased 38%, and basement membrane sleeves decreased 21% over 28 days. Taken together, these findings show that inhibition of PDGF-B signaling can lead to regression of tumor vessels, but the magnitude is tumor specific and does not necessarily retard tumor growth. Loss of pericytes in tumors is an expected direct consequence of PDGF-B blockade, but reduced tumor vascularity is likely to be secondary to pericyte regression. [Cancer Res 2007;67(15):7358-67]

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Section: Methodsmentioning

confidence: 99%

Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells after Inhibition of Platelet-Derived Growth Factor B by Selective Aptamer AX102

et al. 2007

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“…For example, aptamers modified with PEG (40 kDa) and 2′-omethyl resulted in prolonged half-lives. 17, 149, 150, 153 This progress holds promise for overcoming the above challenges and developing aptamers and ApDCs for targeted therapy.…”

Section: Challenges Of Aptamers and Apdcsmentioning

confidence: 99%

Aptamer–Drug Conjugates

2015

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Western medicine often aims to specifically treat diseased tissues or organs. However, the majority of current therapeutics failed to do so owing to their limited selectivity and the consequent “off-target” side effects. Targeted therapy aims to enhance the selectivity of therapeutic effects and reduce adverse side effects. One approach toward this goal is to utilize disease-specific ligands to guide the delivery of less-specific therapeutics, such that the therapeutic effects can be guided specifically to diseased tissues or organs. Among these ligands, aptamers, also known as chemical antibodies, have emerged over the past decades as a novel class or targeting ligands that are capable or specific binding to disease biomarkers. Compared with other types or targeting ligands, aptamers have an array of unique advantageous features, which make them promising for developing aptamer–drug conjugates (ApDCs) for targeted therapy. In this Review, we will discuss ApDCs for targeted drug delivery in chemotherapy, gene therapy, immunotherapy, photodynamic therapy, and photothermal therapy, primarily of cancer.

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“…[167,168] dung 6). [165,[169][170][171][172] Die Analyse und Verbesserung der In-vivoAktivität von in vitro selektierten Aptameren durch eine auf dem Hefe-3-Hybrid-System beruhende Selektion ist kürzlich beschrieben worden.…”

Section: Angewandte Chemieunclassified

Die chemische Biologie von Aptameren

Mayer

2009

Angewandte Chemie

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An einem Strang: Aptamere, kurze einzelsträngige Oligonucleotide mit klar definierter 3D‐Faltung, sind hoch affin und spezifisch für ihre Zielstrukturen und hemmen deren biologische Funktionen. Aptamere können chemisch und/oder enzymatisch hergestellt werden und lassen sich daher als chemische wie auch als biologische Substanzen einordnen. Der aktuelle Stand und neue Entwicklungen auf diesem Gebiet werden vorgestellt.magnified imageAptamere sind kurze einzelsträngige Nucleinsäuren mit einer klar definierten dreidimensionalen Faltung. Sie zeigen eine hohe Affinität und Spezifität für ihre Zielstrukturen und inhibieren deren biologische Funktionen. Aptamere gehören zur Stoffklasse der Nucleinsäuren und können entweder chemisch, enzymatisch oder durch Kombination beider Methoden hergestellt werden. Daher können Aptamere sowohl als chemische wie auch als biologische Substanzen eingeordnet werden. Etablierte Methoden ebenso wie neue Entwicklungen auf dem Gebiet der Aptamere sollen in diesem Aufsatz zusammengefasst werden. Die Verwendung von Aptameren in der chemischen Biologie wird diskutiert.

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Pharmacologic and Pharmacokinetic Assessment of Anti-TGFβ2 Aptamers in Rabbit Plasma and Aqueous Humor

Cited by 34 publications

References 15 publications

Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells after Inhibition of Platelet-Derived Growth Factor B by Selective Aptamer AX102

Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells after Inhibition of Platelet-Derived Growth Factor B by Selective Aptamer AX102

Aptamer–Drug Conjugates

Die chemische Biologie von Aptameren

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