Update on the first phase I study of AGRO100 in advanced cancer

Laber, Damian A.; Sharma, Vivek R.; Bhupalam, L.; Taft, B.; Hendler, F. J.; Barnhart, Kerry M.

doi:10.1200/jco.2005.23.16_suppl.3064

Cited by 28 publications

(19 citation statements)

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“…Thermal denaturation experiments, carried out as described previously (1), indicate that AGRO100 forms a stable structure that melts at 76jC. 6 As shown schematically in Fig. 1, this structure is predicted (2) to be a bimolecular quadruplex that is stabilized by the formation of eight G-quartets.…”

Section: Resultsmentioning

confidence: 80%

“…Following preclinical in vivo studies, which showed that it had no detectable toxicity in normal tissues (5), a truncated version of GRO29A, known as AGRO100 (recently renamed AS1411), has been tested in a phase I clinical trial of patients with advanced cancer. The results of this trial were recently presented (6) and indicated that AGRO100 was well tolerated (no serious adverse effects were observed) and had promising clinical activity.…”

Section: Introductionmentioning

confidence: 74%

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AGRO100 inhibits activation of nuclear factor-κB (NF-κB) by forming a complex with NF-κB essential modulator (NEMO) and nucleolin

Girvan

Teng

Casson

et al. 2006

Molecular Cancer Therapeutics

222

198

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Section: Resultsmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 74%

AGRO100 inhibits activation of nuclear factor-κB (NF-κB) by forming a complex with NF-κB essential modulator (NEMO) and nucleolin

Girvan

Teng

Casson

et al. 2006

Molecular Cancer Therapeutics

222

198

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“…The 26-oligomer DNA aptamer AS1411 is the first aptamer to enter clinical oncology trials. It has shown both promising antitumor activity and a lack of serious systemic toxicity in a phase I clinical trial (Laber et al, 2005). Multi-institutional phase II clinical trials of AS1411 in refractory or relapsed acute myeloid leukemia (AML) (clinicaltrials.gov identifier NCT00512083) and in renal cancer (NCT00740441) are now under way.…”

mentioning

confidence: 99%

Plasma Membrane Nucleolin Is a Receptor for the Anticancer Aptamer AS1411 in MV4-11 Leukemia Cells

Soundararajan

Wang²,

Sridharan³

et al. 2009

Mol Pharmacol

204

156

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AS1411 is a DNA aptamer that is in phase II clinical trials for relapsed or refractory acute myeloid leukemia and for renal cell carcinoma. AS1411 binds to nucleolin, a protein that is overexpressed in the cytoplasm and on the plasma membrane of some tumor cells compared with normal cells. Studies were performed to determine whether cell surface nucleolin is a receptor for AS1411 in the acute myeloid leukemia cell line MV4-11. Biotinylation of MV4-11 cell surface proteins followed by immunoblotting of the biotinylated proteins showed that full-length (106 kDa) and truncated forms of nucleolin were present on the cell surface. In contrast, K-562 cells, which are 4-fold less sensitive than MV4-11 cells to AS1411, showed no full-length nucleolin and lesser amounts of the truncated forms of nucleolin on the cell surface. Incubation of MV4-11 cells with

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“…Ein weiteres Aptamer gerichtet gegen das Protein Nucleolin befindet sich derzeit in Phase-I-Prüfungen für den Indikationsbereich Onkologie [39]. Nucleolin ist normalerweise ausschließlich intrazellulär lokalisiert -, wird aber von Tumorzellen auch auf der Zelloberfläche exprimiert.…”

Section: Aptamereunclassified

“…Bei Bindung des Aptamers an das auf der Zelloberfläche exprimierte Nucleolin kommt es zu einer Internalisierung des Aptamer-Nucleolin Komplexes und anschließendem Zelltod der Tumorzelle. Aufgrund ermutigender erster Phase-I-Daten wurde die Phase I im Dezember 2005 erweitert um zusätzliche Patienten mit Nieren-und Lungenkarzinomen einzuschließen [39].…”

Section: Aptamereunclassified

Oligonukleotid Therapeutika – eine neu entstehende Substanzklasse

Wacheck

2006

Wien Med Wochenschr

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Oligonucleotide therapeutics are short, single- or double-stranded DNA or RNA molecules consisting of strands of 10-50 nucleotides. By targeted modulation of gene expression oligonucleotides provide the chance of targeting diseases at their molecular level. Within this novel emerging class of compounds oligonucleotide therapeutics are discriminated by their structure, function and mode of action. While antisense oligonucleotides, ribozymes and siRNAs suppress the expression of a protein by complementary hybridizing with their target mRNA, aptamers bind like antibodies to their target protein and thereby inhibit its function. Immunostimulatory oligonucleotides are due to sequence motifs within their nucleotide sequence able to trigger a therapeutic exploitable immune response. Currently, there are only two oligonucleotide therapeutics approved by the FDA, namely the antisense oligonucleotide Fomivirsen and the aptamer Macugen. In this review the mode of action of the diverse oligonucleotide therapeutics and their current status in clinical development will be discussed.

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Update on the first phase I study of AGRO100 in advanced cancer

Cited by 28 publications

References 0 publications

AGRO100 inhibits activation of nuclear factor-κB (NF-κB) by forming a complex with NF-κB essential modulator (NEMO) and nucleolin

AGRO100 inhibits activation of nuclear factor-κB (NF-κB) by forming a complex with NF-κB essential modulator (NEMO) and nucleolin

Plasma Membrane Nucleolin Is a Receptor for the Anticancer Aptamer AS1411 in MV4-11 Leukemia Cells

Oligonukleotid Therapeutika – eine neu entstehende Substanzklasse

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