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Abstracts
Heat
shock fusion proteins: A new therapeutic vaccine platform.
Abstract presented at CSSI 2003 Conference held in Quebec, Canada, September 9th to 14th, 2003
L.
Mizzen(1), R. Chu(1), L. Anthony(1), G. Rowse(1), B. Wu(1), H. Liu(1), A.
Recktenwald(1), L. Boux(2), J. Neefe(2), M. Siegel(2).
(1)
Stressgen Biotechnologies Corporation, Victoria, BC, CANADA,
(2)
Stressgen Biotechnologies Inc., Collegeville, PA, USA.
The unusual immunogenicity of Heat shock proteins
(Hsp) has long been recognized. This intense area of research initiated with
the discovery of Hsp as immunodominant B and T cell antigens for a wide
spectrum of microbial pathogens. This lead to their successful preclinical
application as components of prophylactic and therapeutic immunization formats
for infectious disease and cancer. We have captured the immunostimulatory
properties of Hsp in a new therapeutic vaccine format, namely, recombinant Hsp
fusion proteins. These Hsp fusion proteins, which we term CoVal™ fusions, are composed of Hsp covalently fused in-frame
with an antigen against which an immune response is desired, such as a viral or
tumor antigen. We have shown that adjuvant-free immunization of mice with a
variety of CoVal™ fusions results in the induction of antigen-specific, CD8+ cytotoxic T lymphocytes (CTL), and in vitro, production of the Th1 cytokines
IFNγ and TNFα. This profile of immune responses is highly suggestive
of therapeutic benefit against virally infected and transformed cells, which
has been confirmed in different preclinical models. Our lead product based on
this platform, termed HspE7, is composed of Mycobacterium
bovis BCG Hsp65 fused to human papillomavirus (HPV) type 16 E7. In multiple
clinical trials HspE7 has shown activity in the therapy of different
HPV-associated diseases, ie. the precancerous condition anal dysplasia, genital
warts and recurrent respiratory papillomatosis (RRP), which is warts of the
upper airways. Having demonstrated therapeutic activity of our lead product
HspE7 in humans, we are currently developing CoVal™ fusions for other chronic viral infections. Target indications
include HBV, HSV, HCV and HIV.
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