1999
DOI: 10.1016/s0378-4347(99)00285-6
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Detection and plasma pharmacokinetics of an anti-vascular endothelial growth factor oligonucleotide-aptamer (NX1838) in rhesus monkeys

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Cited by 158 publications
(106 citation statements)
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“…Alternatively, because VEGF-Trap also binds mouse VEGF (12), which is not recognized by the anti-VEGF antibody A4.6.1 (13), its greater efficacy could be because of blockade of both tumor-derived (human) as well as host-derived (murine) VEGF. Finally, the increased efficacy of the high-dose VEGF-Trap compared with the VEGF antibody may be because of its ability to bind VEGF family members other then VEGF A, such as placental growth factor, which is known to bind this agent (14). However, we did not test either the NX1838 aptamer or anti-VEGF antibody at higher doses, so it is possible that increased concentrations of these anti-VEGF agents would cause a more complete blockade of tumor growth as well as disrupting cooption.…”
Section: Discussionmentioning
confidence: 99%
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“…Alternatively, because VEGF-Trap also binds mouse VEGF (12), which is not recognized by the anti-VEGF antibody A4.6.1 (13), its greater efficacy could be because of blockade of both tumor-derived (human) as well as host-derived (murine) VEGF. Finally, the increased efficacy of the high-dose VEGF-Trap compared with the VEGF antibody may be because of its ability to bind VEGF family members other then VEGF A, such as placental growth factor, which is known to bind this agent (14). However, we did not test either the NX1838 aptamer or anti-VEGF antibody at higher doses, so it is possible that increased concentrations of these anti-VEGF agents would cause a more complete blockade of tumor growth as well as disrupting cooption.…”
Section: Discussionmentioning
confidence: 99%
“…There were three sets of experiments, each with its own set of control tumors: (i) NX1838, a RNAbased fluoropyrimidine polyethylene glycol-conjugated aptamer targeting human VEGF 165 (NeXstar, Boulder, CO) (13,14) at 250 g per dose NX1838 (n ϭ 5) or vehicle control (0.05% mouse serum albumin, Sigma, n ϭ 5) injected i.p. daily; (ii) humanized monoclonal anti-VEGF antibody (A4.6.1, Genentech) (11), at 100 g͞dose (n ϭ 19) or vehicle control (n ϭ 21) administered i.p.…”
Section: Methodsmentioning
confidence: 99%
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“…This effect should only be enhanced by the optimization of this aptamer for in vivo applications. For instance, modification of 11-1.41 with 2Ј-fluoro-pyrimidines and addition of the 3Ј inverted nucleotide cap improve resistance to degradation by plasma nucleases (38,39), but the truncated aptamer's small size (Ϸ13 kDa) allows rapid tissue diffusion and renal clearance (40,41). Therefore, modifications such as attachment of polyethylene glycol or liposomes, which enhance aptamer bioavailability, will likely enhance the aptamer's efficacy for both local and systemic applications in relevant disease models.…”
Section: Discussionmentioning
confidence: 99%
“…Both DNA and nuclease-resistant RNA aptamers against human L-selectin have been shown to inhibit human lymphocyte trafficking in severe combined immunodeficient (SCID) mice (46,47). The most progress has been made with a polyethylene glycol-conjugated version of a nuclease-resistant RNA aptamer against VEGF, which has now shown promising results in both preclinical and clinical studies for the exudative form of agerelated macular degeneration (41,48,49).…”
Section: Discussionmentioning
confidence: 99%