Aptamer : Toxin conjugates that specifically target prostate tumor cells

We have used RNA aptamer:gelonin conjugates to target and specifically destroy cells overexpressing the known cancer biomarker prostate-specific membrane antigen (PSMA). Aptamer:toxin conjugates have an IC50 of 27 nmol/L and display an increased potency of at least 600-fold relative to cells that do...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006-06, Vol.66 (12), p.5989-5992
Main Authors: CHU, Ted C, MARKS, John W, LAVERY, Laura A, FAULKNER, Sarah, ROSENBLUM, Michael G, ELLINGTON, Andrew D, LEVY, Matthew
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacokinetics
Aptamers, Nucleotide - genetics
Aptamers, Nucleotide - pharmacokinetics
Biological and medical sciences
Cell Line, Tumor
Drug Delivery Systems - methods
Gynecology. Andrology. Obstetrics
Humans
Inhibitory Concentration 50
Male
Male genital diseases
Medical sciences
Nephrology. Urinary tract diseases
Pharmacology. Drug treatments
Plant Proteins - administration & dosage
Plant Proteins - pharmacokinetics
Prostate-Specific Antigen - biosynthesis
Prostate-Specific Antigen - genetics
Prostate-Specific Antigen - metabolism
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Ribosome Inactivating Proteins, Type 1
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
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Summary:We have used RNA aptamer:gelonin conjugates to target and specifically destroy cells overexpressing the known cancer biomarker prostate-specific membrane antigen (PSMA). Aptamer:toxin conjugates have an IC50 of 27 nmol/L and display an increased potency of at least 600-fold relative to cells that do not express PSMA. The aptamer not only promotes uptake into target cells but also decreases the toxicity of gelonin in non-target cells. These results validate the notion that "escort aptamers" may be useful for the treatment of specific tumors expressing unique antigen targets.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-05-4583