By Matthew Willett
Ariad Pharmaceuticals Inc. reported on the application of its Argent gene regulation technology for eradication of tumor cells derived from neuroblastomas, prostate and breast malignancies.
Three presentations Thursday at the fourth annual American Society of Gene Therapy meeting in Seattle detailed Ariad¿s Argent system, which activates cell-death switches using small-molecule therapeutics.
Tim Clackson, Ariad¿s vice president of gene therapy, said his company¿s platform differs from others in that it¿s focused on regulation, not delivery.
¿The Argent system is a method for controlling the activity of cells by virtue of activating genes or proteins in those cells using a small molecule,¿ he told BioWorld Today. ¿It¿s a way of regulating cellular events that are critical for gene and cell therapy.¿
Argent uses small molecules to turn on or off genes delivered by the most convenient and functional vector available: retroviral, adeno-associated viral or lentiviral vectors. Clackson said that makes the system more dose specific.
¿In the case of gene therapies, a lot of [investigators] are interested in using a gene therapy to deliver a therapeutic protein, in which the gene is introduced in patients and that gene leads to the production of a protein,¿ Clackson explained. ¿What Argent allows us to do is control the expression of the drug using a small-molecule drug, and that gives us a much greater degree of control over the dosage of the protein, the delivery and the timing of the dose and, crucially, one is able to turn off the drug delivery at will, in contrast to unregulated therapies where one has no control.¿
Ariad told meeting attendees the system effectively killed tumor cells engineered to express specific cell-death switches, and that Argent cell-death technology significantly slowed the progression of prostate tumors in vivo in an animal model.
Two additional presentations reported on the Argent system¿s use for regulating a highly toxic antitumor therapy named fusogenic membrane glycoproteins, a class of highly potent antitumor proteins.
Administration of fusogenic membrane glycoproteins requires tightly controlled gene expression, Ariad, of Cambridge, Mass., said. A separate study by the same team, the company said, used the Argent system to develop hybrid viruses that can be used to treat cancer.
Still other programs from Ariad collaborators detailed progress in programs using Argent cell-growth switches for stem cell therapies. An animal study by researchers at the University of Washington indicated that the use of Argent technology selectively induced growth in a population of blood cells expressing the gamma globin gene at high levels in vivo. Hemoglobinopathies due to the mutation of the gamma globin gene include thalassemia and sickle cell anemia.
Ariad¿s cell regulation program is its most advanced clinically, Clackson said. A product for treatment of graft-vs.-host disease that eliminates T cells through regulated cell death in association with bone marrow transplant procedures has completed a Phase I safety trial, and Clackson said Ariad plans to move the program into Phase II trials in a variety of cancers.
The regulated stem cell therapy program, he said, is in preclinical study, and a regulated gene therapy project for production of erythropoietin for treatment of anemia is in late-stage preclinical testing. Clackson said Ariad plans to move that program into Phase I testing within a year.
Ariad¿s stock (NASDAQ:ARIA) rose significantly in early trading Thursday, ending the day up 15 percent, or 77 cents, at $5.90.
In other news from the meeting:
¿ Chromos Molecular Systems Inc., of Burnaby, British Columbia, is presenting data on the development of its chromosome-based platform technology for gene therapy. Chromos said the platform technology can be used for stable delivery and expression of a wide range of large genes or multiple gene targets.
¿ Genzyme Corp., of Cambridge, Mass., updated in 17 presentations progress in its gene therapy program focused on potential treatments for genetic diseases, cardiovascular diseases and cancer. Presentations included updates on the company¿s gene therapy program for treatment of Fabry disease, which showed proof of concept and feasibility in preclinical studies, and the use of therapeutic angiogenesis for treatment of ischemic heart disease and peripheral vascular disease, the inhibition of post-angioplasty restenosis and treatment of Gaucher disease.
¿ Targeted Genetics Corp., of Seattle, presented data from its joint venture with Elan Corp. plc, of Dublin, Ireland, Emerald Gene Systems. The company said data describe enhancements that enable cellular targeting with TGC¿s proprietary LPD (Lipid-Protamine-DNA) gene delivery system. The data showed significant dose-dependent increases in cell binding and gene expression in tissue culture, increases from 100- to 285-fold.
¿ Vical Inc., of San Diego, reviewed safety data from its Allovectin-7 and Leuvectin trials. Vical¿s scientists also presented data indicating naked DNA protein expression levels improved due to the use of electroporation and poloxamers. Data from 15 completed studies and encompassing more than 560 patients indicated that the Allovectin-7 and Leuvectin treatments produced severe reactions in 1 percent of treated patients.