To: tuck who wrote (68 ) 9/26/2002 2:31:36 PM From: tuck Read Replies (2) | Respond to of 510 >>FREMONT, Calif., Sept. 26 /PRNewswire-FirstCall/ -- Ciphergen Biosystems, Inc. (Nasdaq: CIPH - News) today announced an important discovery made using their proprietary protein analysis technology: the long-awaited identification of the CD8+ Antiviral Factor (CAF), responsible for suppressing HIV-1 replication. This discovery, made in collaboration with the Aaron Diamond AIDS Research Center (ADARC), was released online today by the journal Science at the Science Express website ( scienceexpress.org ). A small percentage of HIV-infected individuals do not develop AIDS, even after many years. Those HIV-infected individuals who remain healthy are termed "long-term non-progressors" (LTNP), and it has been long thought that a soluble factor secreted by CD8+ cytotoxic T lymphocytes might play a role in the differing course of their disease. The suppressive activity of CAF has been demonstrated to control the productive infection of both CD4+ T cells and macrophages infected with HIV-1, irrespective of viral phenotype. Importantly, the CAF-associated antiviral activity has been shown to correlate positively with higher CD4+ T cell count, improved clinical status, and in particular, non-progression over long periods of HIV-1 infection. First described in 1986, numerous AIDS research groups worldwide have worked over the intervening 16 years to attempt to discover the identity of CAF, employing a wide range of technologies and approaches. On February 14, 2002, Ciphergen and ADARC signed a Research and License Agreement focusing on this same objective. As part of the Agreement, Ciphergen retains therapeutic and diagnostic rights to discoveries made under the collaboration, with royalties back to ADARC. William Rich, President and CEO of Ciphergen commented, "Ciphergen is honored that our scientists and technology have helped facilitate the solving of such an important scientific and clinical problem with the Aaron Diamond AIDS Research Center. We're gratified by the exceptional speed of our progress so far and look forward to further supporting ADARC as we continue follow-up research studies." Dr. David Ho, Scientific Director and CEO of ADARC, stated, "Ciphergen's ProteinChip System was essential in the discovery, identification and characterization of these proteins. We look forward to continuing to work with Ciphergen to advance our understanding of this important phenomenon." The Science paper released today reports use of Ciphergen's SELDI ProteinChip® System to identify alpha defensins-1, -2, and -3 as molecules with CAF antiviral activity. Using the SELDI ProteinChip System, the joint research team compared protein expression patterns of CD8+ T lymphocytes from LTNP, HIV-infected normally progressing patients and uninfected individuals, and found a cluster of low molecular weight differentially secreted peptides. Using an antibody-capture experiment followed by ProteinChip System analysis as well as protein sequencing using a Tandem Mass Spectrometer outfitted with Ciphergen's ProteinChip Interface, the researchers have provided convincing evidence that these proteins belong to members of the human alpha defensin family. The research team also demonstrated by in vitro culture that alpha defensins constitute the suppressive activity against HIV-1 observed in the supernatant from stimulated CD8+ T lymphocytes of LTNP that is not attributable to beta-chemokines. The researchers therefore conclude that human alpha defensin proteins are primarily responsible for the suppressive activity of CAF against HIV-1 replication. Having identified human alpha defensins-1, -2 and -3 as CAF, it should now be easier to determine the specific subpopulation of CD8+ T cells that is producing these antiviral factors and to confirm the mechanism of action responsible for this antiviral activity. The mechanism of action of defensins in HIV-1 is not precisely known at this point, although previous studies on CAF have suggested an effect on viral transcription. If verified, this would constitute a mechanism of action that is quite different from existing AIDS treatments and present possible new therapeutic strategies.<< snip I just now nibbled some CIPH. Cheers, Tuck