Aptamer : Toxin conjugates that specifically target prostate tumor cells

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 12; pp. 5989 - 5992
• Main Authors: CHU, Ted C, MARKS, John W, LAVERY, Laura A, FAULKNER, Sarah, ROSENBLUM, Michael G, ELLINGTON, Andrew D, LEVY, Matthew
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.06.2006
• 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; Toxin; Prostate tumor; Urinary system disease; Prostate disease; Aptamer; Target cell; Conjugated compound; Male genital diseases; Tumor cell
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-4583

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.