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NeXstar Creates Aptamer-Based Diagnostic Assay; Assay Aids Clinical Development of VEGF Inhibitor
BOULDER, COLORADO, AUGUST 6, 1996 -- NeXstar Pharmaceuticals, Inc., (NASDAQ:NXTR) announced today that it has successfully developed a new analytical method that uses aptamers to detect small amounts of clinically important substances. This technique, named the enzyme-linked oligonucleotide assay, or ELONA, not only has applications in standardized-format clinical assays, but is also playing an important role in the Company's on-going development of its angiogenesis inhibitors as anti-cancer agents. Aptamers are short, rigid oligonucleotides that recognize target molecules with high affinity. NeXstar Pharmaceuticals is creating aptamers for both therapeutic and diagnostic applications using its patented SELEX combinatorial chemistry process.The August issue of the journal Nature Biotechnology has published an article describing the ELONA system, in which an aptamer replaces an antibody in the enzyme-linked assay diagnostic assay format known as ELISA. The article, titled "An enzyme-linked oligonucleotide assay," was authored by Daniel W. Drolet, Ph.D., Lotus Moon-McDermott and Timothy S. Romig, all of NeXstar Pharmaceuticals.
In a typical ELISA, one antibody is used to capture the substance to be measured and anchor it to a surface, typically in a microtiter plate. A second antibody, coupled to a detect reagent, is then added and is used to measure the quantity of substance present. Antibodies, while excellent diagnostic reagents in general, do have limitations. Some target molecules are poorly immunogenic or toxic, making it difficult or impossible to raise an antibody. The large size and complexity of a typical antibody can make it difficult to modify the antibody with the reagents needed for detection or can interfere with the speed with which the assay can be run.
In the current work, Dr. Drolet and his colleagues used an aptamer that binds specifically and tightly to human vascular endothelial growth factor (VEGF), a protein secreted by tumors that triggers the growth of new blood vessels. The aptamer was modified by attaching a reagent used frequently in ELISA to measure the amount of binding that occurs, and it was then used as the detect reagent. Measures of precision, accuracy, interference, and specificity showed that this aptamer-based assay was equivalent to a typical ELISA using an antibody as the detect reagent. It should be possible to develop an aptamer that would replace the capture antibody, too.
"This paper demonstrates the utility of aptamers generated using our SELEX process in an important diagnostic format," said Barry A. Polisky, Ph.D., NeXstar Pharmaceuticals' Vice President for Drug Discovery. "This performance, coupled with the advantages that aptamers have over monoclonal antibodies, suggests that aptamers may have important applications in the diagnostic arena." Last week, NeXstar Pharmaceuticals and Roche Molecular Systems signed a research and development agreement that calls for NeXstar Pharmaceuticals to develop an aptamer for use in the PCR DNA amplification process.
In addition, the Company believes that the VEGF ELONA will play an important role in the clinical development of its VEGF antagonist, a compound that has already demonstrated promising in vitro and in vivo activity. There is a large body of published data demonstrating that tumor-directed angiogenesis is a heterogeneous process: not all tumors trigger blood vessel growth using the same angiogenesis factor. This heterogeneity means that not all cancer patients may be candidates for treatment with a drug directed against one specific angiogenesis factor. Thus, the Company's parallel development of the VEGF ELONA and a therapeutic based on an anti-VEGF aptamer may improve the design of clinical trials that will test the efficacy of such an aptamer. The Company is also developing inhibitors of other angiogenesis factors, including PDGF, TGF-beta and the integrin alpha-v-beta-3, and will create ELONAs for each of these antagonists as needed.
NeXstar Pharmaceuticals, Inc. is an integrated pharmaceutical company engaged in the discovery, development, manufacturing and marketing of products to treat life-threatening diseases. The Company currently markets two drugs, AmBisome and DaunoXome. The Company has headquarters in Boulder, Colorado; research, development and manufacturing facilities in San Dimas, California; Antwerp, Belgium; Lakewood, Colorado, and Boulder; and marketing subsidiaries worldwide.
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