Advertisement
Results: Data from the study not only confirmed that the addition of theTLR3 agonist Poly IC potently alters the magnitude of the antigen-specific CD8effector arm, but also that adding this moiety acts to push the immuneresponse into a more potent Th1-biased response. This was demonstrated by asignificant reduction of Interleukin-5 (IL-5) levels seen followingimmunization with HspE7 co-administered with Poly IC, compared to those seenwith HspE7 alone. Importantly, the IL-5 decrease was accompanied by asignificant increase in the level of Interferon-gamma (IFN-gamma) in the PolyIC-containing HspE7 formulations. IFN-gamma is a hallmark cytokine associatedwith the generation of Th1-biased immune responses. In addition to the shiftfrom IL-5 to IFN-gamma, there was also a significant increase in thegeneration of antigen-specific IL-2-secreting CD4 helper T cells. In thestudy, IgG1, IgG2b and IgG2c antibody responses were dramatically increased aswell by the incorporation of Poly IC to the immunization.
Advertisement
Dr. Peter Emtage commented on the data: "Taken together, theantigen-specific increase in CD8 responses, CD4 helper T cell-derivedcytokines, and the antigen-specific increase in IgG2b and IgG2c antibodyisotypes, all clearly demonstrate a potentiated Th1 immune response to thecombination of HspE7 and Poly IC. With our HPV fusion candidate in Phase 1clinical development using a Poly IC-containing adjuvant, we believe thesedata suggest the potential for greater efficacy of HspE7, given that increasedTh1 immune responses typically translate to more balanced and significantlymore potent antiviral and/or anti-tumor activity."
Background: The development of the appropriate immune response by a hostto an invading pathogen is critical for the control and elimination of thepathogen. All therapeutic vaccines attempt to recapitulate an anti-pathogenresponse by utilizing antigenic fragments from the infectious agent to educatethe immune system. This education results in the targeting of the pathogen bythe effector arms of the host's immune system. Unfortunately, most often intherapeutic vaccine development, the magnitude of the immune response is lessthan desired to effect significant change at the site of infection, be itchronic or acute. To develop a more robust vaccine strategy, the field hasturned to antigen delivery approaches (e.g. viral and DNA) to "boost" theinitial immune response to levels more appropriate for therapy. An alternativeapproach is the use of biological response modifiers or adjuvants. With theidentification of agonists to the Toll-like receptor (TLR) pathways, it hasbecome possible to not only enhance the magnitude of the immune response, butalso to induce the type of response that favors the mechanism of action thatis needed to clear the infection.
Nventa has previously shown that HspE7, a proprietary therapeutic vaccinecomprised of a heat shock protein (Mycobaterium bovis BCG Hsp65) linked to theE7 protein of HPV type 16, when combined with the TLR3 agonist Poly IC, iscapable of inducing potent E7-specific CD8 T cell responses (cellularresponses) and regressing established E7-expressing tumors in mice. In thisnew study presented today, the Company investigated wh
