[CpG-rich DNA conjugates/ragweed/Dynavax]
EMERYVILLE, Calif., March 20 /PRNewswire/ -- An anti-allergy therapy under development at Dynavax Technologies Corporation proved effective in reversing an established allergic response to ragweed pollen in mice, according to a paper published in the March issue of the Journal of Allergy and Clinical Immunology, Volume 109, #3. The paper provides positive evidence of the potential role that this therapy may play in the treatment of human allergic disorders, including asthma.
According to lead author, Marsha Wills-Karp, Ph.D., of the Division of Immunobiology at the Cincinnati Children's Hospital Medical Center, ``The paper presents the first demonstration that the novel therapy may actually reverse airway responsiveness, a hypersensitivity of the lungs associated with asthma. Prior studies showed that Dynavax's ImmunoStimulatory DNA sequences (ISS) containing CpG motifs could prevent the development of allergic airway responses in murine models, but until now, no study had evaluated the ability of ISS to reverse the condition. This finding gives us greater confidence about the compound's potential as a potential asthma therapy.''
In the study reported in Journal of Allergy and Clinical Immunology, mice were sensitized and challenged with ragweed pollen extract, and then treated intradermally twice at one-week intervals with Dynavax's immunostimulatory oligodeoxynucleotide (ISS) chemically linked to Amb a 1 (Amb a 1-ISS). One week after treatment, the mice were rechallenged intratracheally with ragweed extract and airway responses were measured.
The results showed that after sensitization, treatment with Dynavax's AIC (Amb a 1-ISS) significantly reduced asthma symptoms, including airway hyper-responsiveness and eosinophilia induced by subsequent pulmonary allergen challenge. AIC also significantly increased allergen-specific IgG antibody responses and interferon (IFN) gamma responses compared to those of untreated animals or animals treated with native allergen. IFN gamma is a key cytokine involved in Th1 responses. IgG is a class of antibody typically associated with non-allergic immune responses. The paper's author noted that, ``Interestingly, the inhibitory effect of Amb a 1-ISS on allergen-driven airway hyper-responsiveness was independent of suppression of Th2 cytokine production,'' indicating that the compound had in fact reprogrammed the immune system and down-regulated a potentially harmful response to ragweed allergen.
``We are excited by these new preclinical data confirming AIC's ability to reprogram immune responses and modify allergic conditions in animals,'' stated Gary Van Nest, PhD., Dynavax Vice President of Preclinical Research. ``Recently we have begun to see significant indications that this approach may provide a safe and effective therapy for other allergic disorders, including rhinitis, in humans.''
Dynavax's proprietary technology platform is based upon a unique short immunostimulatory sequence of single-stranded DNA, termed ISS. AIC is a new therapeutic drug combining the company's ISS technology with Amb a 1, the main allergen in ragweed pollen, in order to divert the immune system response away from harmful allergic reactions to ragweed -- thereby potentially relieving the inflammatory symptoms associated with allergic rhinitis. Other pre-clinical studies have suggested that AIC induces an enhanced Amb a 1-specific, Th1-type response, possibly reprogramming the immune system away from the strong Th2 response associated with allergic inflammation and histamine release -- both of which are implicated in asthma.
AIC is Dynavax's lead product. It has been studied in eight clinical trials, three of which were Phase II studies completed in 2001 in Canada, France, and the U.S. |
