By Brady Huggett
EntreMed Inc. reported news Friday concerning its work with Cell Genesys Inc. and separate news through its majority-owned subsidiary, TheraMed Inc., at the 4th annual meeting of the American Society of Gene Therapy in Seattle.
The preclinical data from Foster City, Calif.-based Cell Genesys and EntreMed, of Rockville, Md., demonstrated the feasibility of gene therapy as a strategy to inhibit tumor growth by delivering genes that block the growth of tumor blood vessels. The studies combined Cell Genesys¿ proprietary adeno-associated viral (AAV) and adenoviral gene delivery systems to deliver EntreMed¿s Angiostatin and Endostatin to lung tumors in a mouse tumor model.
The data showed a 60 percent inhibition of lung tumor growth when Angiostatin was delivered with an adenoviral vector. When either Angiostatin or Endostatin was administered using the AAV vector, a 50 percent inhibition of tumor growth was seen, and with the most potent combination of AAV-Angiostatin administered, a more than 80 percent reduction in tumor metastases was seen, compared to mice not receiving treatment.
TheraMed Inc. presented data demonstrating cell-specific gene delivery using its technology for drug and gene insertion into human blood cells. The company said the data confirm TheraMed¿s ability to deliver therapeutic proteins without the risks associated with viral gene delivery. TheraMed¿s system is used for ex vivo modification of primary human blood cells.
In other news from the meeting:
¿ Ariad Pharmaceuticals Inc., of Cambridge, Mass., said sustained, therapeutic levels of erythropoietin continue to be produced following intermittent doses of Ariad¿s small-molecule drug three years after an intramuscular injection of vectors containing the genes for EPO and the Argent gene regulation technology in a nonhuman primate model. It said the data show an advance in the preclinical development of its regulated protein therapy product to treat anemia.
¿ Copernicus Therapeutics Inc., of Cleveland, presented data showing its compacted DNA formulation can effectively transfect nondividing human cells. The compacted DNA nanoparticles transfect post-mitotic human cells, achieving up to a 6,900-fold enhancement of gene expression compared to naked DNA, the company said.
¿ Crucell NV, of Leiden, the Netherlands, presented data demonstrating its new AdVac vaccination system provides a stronger immune response with improved safety. The AdVac system is based on the adenovirus serotype 35 and the data showed the new AdVac vector binds to and transduces cells that elicit a strong immune response, the company said.
¿ GenStar Therapeutics Corp., of San Diego, presented preclinical data on its gene delivery system, Maximum Adenovirus. The administration of its MAX-AD Factor VIII treatment for hemophilia A, in conjunction with mild immune suppressors, resulted in increased and sustained therapeutic levels of Factor VIII protein for the treatment of hemophilia A. The MAX-AD Factor VIII gene therapy product for hemophilia is a gene delivery system derived from the adenovirus.
¿ RHeoGene LLC, of Charlottesville, Va., presented new results from ongoing research that has created new forms of ligand-inducible, chimeric receptors. The company said the receptor modifications will improve the sensitivity, precision and level of gene expression in mammalian cells. RheoGene¿s RHeoSwitch inducible gene expression technology systems turn gene expression on and off and pair its RHeoChem ligand inducers with RHeoCept receptor proteins.
¿ Sangamo BioSciences Inc., of Richmond, Calif., presented data demonstrating Sangamo¿s engineered zinc finger DNA-binding protein transcription factors (ZFP TFs) induced blood vessel growth in animal models. The initial data support the potential use of ZFP TFs in the treatment of certain cardiovascular and peripheral vascular diseases. Edwards Lifesciences Corp., of Irvine, Calif., funded the research.
¿ Targeted Genetics Corp., of Seattle, presented data from a repeat-dosing study of aerosolized tgAAVCF in nonhuman primates. The product is being co-developed with Celltech Group plc, of Slough, UK. The data demonstrated a dose-dependent gene transfer, detectable gene expression in five of eight vector-treated animals, a limited extra-pulmonary biodistribution pattern with no distribution to the gonads and sustained levels of vector over multiple doses. A Phase II repeat-dosing study of aerosolized tgAAVCF in patients with cystic fibrosis is ongoing and more than 70 patients have received it to date.