CAMBRIDGE, Mass., Sept. 26 /PRNewswire-FirstCall/ -- Hybridon, Inc. (OTC Bulletin Board: HYBN - News) announced today that its researchers have published data on novel DNA molecules that stimulate the immune system with increased potency and selectivity. These molecules, which utilize a proprietary structure, have the potential to combat a wide variety of disease conditions, including cancer, infectious disease and asthma/allergies.
The in vitro and in vivo research data, published in the September, 2002 issue of Biochemical and Biophysical Research Communications, show that these second-generation synthetic CpG immunomodulators have significantly increased metabolic stability as compared to the native compound, and induce higher secretion of disease fighting IL-12, with minimal induction of pro-inflammatory IL-6. The paper further discusses using Hybridon's chemistries to design molecules that would stimulate the induction of other cytokines in a selective manner to treat specific diseases. In effect, the Hybridon molecules are intentionally causing a shift between the two types of immune response, the so-called Th-1 and Th-2 responses, towards Th-1, thereby allowing more effective treatment of certain disease conditions.
"This work of Hybridon's scientists and their collaborators at the University of Alabama at Birmingham is a highly promising advance in the development of potent, specific and tolerable immunomodulatory molecules," said James B. Wyngaarden, M.D., Hybridon's Chairman. "There is a great demand in the medical community to use the body's immune system to fight disease. These molecules may be able to address that demand, either as monotherapies, or by making other agents more effective and/or less toxic."
"The synthetic CpG compounds reported represent another milestone by Hybridon scientists in the development of novel second-generation oligonucleotide chemistries," added Stephen R. Seiler, Hybridon's Chief Executive Officer. "In addition to our well known antisense platform, we now have a growing platform of advanced synthetic immunomodulatory oligonucleotide (IMOTM) compounds. Hybridon has already licensed its second-generation antisense chemistry to six companies, including a broad license to Isis Pharmaceuticals, and, as recently announced, selective licenses to Micrologix Biotech and Aegera Therapeutics. We intend to aggressively pursue additional partnerships with both our antisense and IMO technology platforms."
The research describes a novel design of native backbone DNA structure by attaching two short CpG DNA molecules through their 3' -ends. In murine models, this design permits greater stability against DNA digesting enzymes in serum without requiring phosphorothioate backbone modification or poly(dG) structures that are commonly used, but have various limitations associated with them. The Hybridon molecules activate one of the transcription factors, NF-kB, that is responsible for upregulation of cytokine gene expression. However, by virtue of their design, they selectively induce higher IL-12 secretion with only minimal IL-6 secretion.
As a result of the above mentioned properties, these novel CpG DNA molecules show potent anti-tumor activity in tumor xenograft models in nude mice. In addition, because of their ability to selectively induce IL-12 secretion and thereby gamma interferon, they may find wide application as co- therapies with vaccines and monoclonal antibodies for a number of other disease conditions, and as treatments for asthma and allergic conditions alone or in combination with antigens.
The discussed paper is entitled "Potent CpG oligonucleotides containing phosphodiester linkages: in vitro and in vivo immunostimulatory properties," and appeared in Biochemical and Biophysical Research Communications 297 (2002) 83-90. |
