Aug. 23 /PRNewswire/ -- Cell Genesys, Inc. (Nasdaq: CEGE - news) announced today, in collaboration with GPC Biotech AG (Frankfurt: GPC) that a novel gene therapy employing a unique, proprietary fusion gene, referred to as p27/p16, was capable of killing multiple cancer cell types in preclinical studies. Of particular significance was that tumor cell death was induced in twelve of fourteen human tumor cell types regardless of whether the cells contained a normal or mutated p53 gene-a naturally occurring tumor suppressor gene which typically protects against cancer but is mutated in more than 50 percent of all human cancers. Additionally, the tumor cell killing with p27/p16 gene therapy was selective and did not affect surrounding normal tissue. These data were published in the August issue of the journal, Molecular Therapy, by James G. McArthur, Ph.D., and colleagues at Cell Genesys and GPC Biotech.
In the reported work, a number of preclinical studies were conducted to evaluate gene therapy with p27/p16, a unique fusion gene comprised of two cell cycle inhibitory genes, p27 and p16, which control tumor growth by blocking tumor cell division and inducing tumor cell death. In a series of studies in human tumor models in mice, the p27/p16 gene was delivered to the tumor using an adenoviral gene delivery system. Gene therapy with the p27/p16 fusion gene blocked tumor progression in approximately 50 percent of the treated animals, a result that was highly statistically significant in these experiments (p= .002). The fusion gene demonstrated five to 50-fold greater tumoricidal activity than either of the individual p16 and p27 genes. In addition, p27/p16 gene therapy demonstrated microscopic evidence of an antiangiogenic effect against the tumor with inhibition of tumor blood vessel formation.
``We are encouraged by the preclinical studies performed to date with p27/p16 gene therapy particularly with respect to the breadth of antitumor activity and selectivity for tumor as opposed to normal cells,'' stated Joseph J. Vallner, Ph.D., executive vice president and chief operating officer at Cell Genesys. ``The success of this program together with our expanding research efforts in cancer gene therapy involving antiangiogenesis demonstrates Cell Genesys' growing pipeline of potential cancer products and is an important complement to our program in human clinical trials of GVAX® cancer vaccines.''
``This project exemplifies the substantial value of GPC Biotech's extensive estate of issued patents in the field of tumor suppressor genes and growth control, including p27/p16 which is derived from the tumor suppressor genes p16 and p27 and was originally engineered by scientists at Mitotix Inc., now GPC Biotech Inc. In the hands of Cell Genesys with its world class expertise in gene therapy, the p27/p16 fusion gene has exciting potential in the treatment of both cancer and cardiovascular disease,'' stated Muzammil Mansuri, Ph.D., executive vice president and chief operating officer for GPC Biotech's Cambridge, MA site.
In 1998, Cell Genesys exclusively licensed a family of cell cycle inhibitor genes from Mitotix, Inc., which was recently acquired by GPC Biotech AG (Munich, Germany). The licensed genes include p16, p27 and novel p27/p16 fusion genes. The collaboration was initially focused on the development of cardiovascular gene therapy products and was expanded to include cancer gene therapy products in 1999. The p16 and p27 cell cycle inhibitor genes, also referred to as cyclin dependent kinase inhibitors (CDKi), play a key role in the regulation of cellular division. Moreover, the p16 gene, a known tumor suppressor gene, has been shown to be missing or mutated in many important cancers. Gene therapy employing p16, p27 and/or the p27/p16 fusion gene could therefore potentially be used to treat a variety of cancers. In addition, such gene therapy may have applicability to the treatment of other diseases characterized by abnormal cell growth such as restenosis, a condition resulting from the excessive growth of blood vessel smooth muscle cells which can arise after angioplasty for coronary artery disease and other cardiovascular disorders. GPC Biotech and Cell Genesys have an ongoing research collaboration for the optimization and testing of the p16, p27 and p27/p16 fusion genes. |
