BERKELEY, CA (December 15, 1998): Injections of proprietary immunostimulatory DNA sequences (ISS-DNA), under development by Dynavax Technologies Corporation, can alter the nature of the immune response in allergic asthma, while also inhibiting the symptoms of that disease, the company announced. Dynavax scientists and their collaborators published research in the December 15 issue of the Journal of Immunology showing that a single systemic or mucosal (intranasal or intratracheal) administration of ISS-DNA in an animal model of allergic asthma inhibited disease symptoms as effectively as systemic corticosteroids administered daily for seven days. Moreover, unlike the corticosteroids, ISS-DNA injections were able to redirect the immune response away from the strong Th2 response associated with allergic inflammation toward a non-allergic Th1 response.
"This study demonstrates in vivo, for the first time, that ISS-DNA can be used as a drug to both inhibit and modify allergic disease," said Dino Dina, M.D., president and chief executive officer of Dynavax. "In fact, our lead ISS-DNA molecule has proven active in every animal species that Dynavax scientists and their collaborators have tested to date, including primates. Based on their research, we believe that ISS-DNA therapy may provide a totally novel, highly effective therapy for chronic allergic pulmonary inflammation."
The Journal of Immunology study was authored by Dynavax founder, Eyal Raz, M.D. and David Broide, M.B. Ch.B. of the Department of Medicine, University of California, San Diego; and their collaborators Helen Tighe, Ph.D., Minh-Duc Nguyen, and Siamak Malek at Dynavax; Tim Gifford and John Van Uden at the University of California, San Diego; and Jurgen Schwarze, M.D. and Erwin W. Gelfand, M.D. at the Department of Pediatrics, National Jewish Medical and Research Center in Denver, CO.
In the study, the researchers used a mouse model of allergen-induced airway hyperresponsiveness to investigate whether ISS-DNA could inhibit the generation of Th2 cytokines (IL-5, GM-CSF, IL-3) important to the proliferation and survival of white blood cells involved in inflammation (eosinophils). They also examined the effect of ISS-DNA on subsequent airway hyperreactivity in response to an allergic challenge. The researchers' results showed that administration of ISS-DNA inhibited both airway hyperresponsiveness and eosinophil infiltration by exerting a significant inhibitory effect on the generation of eosinophil-active cytokines (IL-5, GM-CSF and IL-3). Moreover, while both ISS-DNA and corticosteroids inhibited IL-5 generation, only ISS-DNA was able to induce IFN-g, a cytokine that biases the immune system to generate a Th1 (and not Th2) response to subsequently encountered allergens.
Dynavax's proprietary ISS-DNA represents a broad technology platform for modulating immune system responses that has applications to a large number of medically important disease states. Based on this platform, Dynavax is focusing its initial development efforts on generating new therapeutics for the treatment or prevention of allergies and asthma. Additionally, the company plans to collaborate with major corporate partners to apply its technology in other key areas. For example, Dynavax technology is uniquely suited for use in enhancing the ability of current and new infectious disease vaccines to produce effective immune responses. Similarly, the ability of ISS-DNA to modulate the immune response should enable the development of more effective therapies for chronic infectious diseases and cancer. Dynavax's technology also provides opportunities to intervene directly in inflammatory and autoimmune disease processes, thus offering unique alternatives to current symptomatic treatments.
Dynavax has developed a strong patent portfolio including allowed patents and patent applications. The company has key proprietary positions on ISS sequences that are active in multiple species including primates and on the use of those sequences in allergy and asthma, and for enhancing responses to infectious disease and cancer antigens. Dynavax has also filed multiple patents covering the use of ISS-DNA to suppress Th2 and enhance Th1 immune responses.
Dynavax Technologies Corporation, a privately held biotechnology company, was founded in 1996 to discover and develop products to treat or prevent disease based on proprietary DNA molecules and their use in modulating immune systems responses.
Contact:
Dino Dina, M.D. President and CEO
Dynavax Technologies Corp. 510-848-5100
Media Contact:
Joan Kureczka
J. Kureczka Associates 415-821-2413
Journal
The Journal of Immunology