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Abstracts
Memory
CD8+ T cells induced by HspE7 fusion protein provide protection against tumor
challenge
Abstract presented at the Keystone Symposia: Basic Aspects of Tumor Immunology held in Keystone, CO March 19th to 24th, 2005
H
Liu(1), G Rowse(1), B Wu(1), A Recktenwald(1), M Siegel(2)
(1) Stressgen Biotechnologies, Victoria, BC, Canada
(2)
Stressgen Biotechnologies Inc., Collegeville, PA, U.S.A.
Scientific
Rationale:
Infection with human papillomavirus type 16
(HPV16) is strongly associated with a variety of anogenital cancers. It is believed that induction of T
cell-mediated immunity, particularly cytotoxic T lymphocytes (CTL), is
important in the eradication of HPV-induced lesions. Previous studies have shown that heat shock protein (Hsp) fusion
proteins are capable of inducing potent antigen-specific CTL activity in
experimental animals. In addition, the
outgrowth of E7-expressing murine tumor cells (TC-1) in vivo can be
prevented by treatment of mice with HspE7, an Hsp fusion protein comprised of Mycobacterium
bovis BCG Hsp65 linked to HPV16 E7. Moreover, HspE7 has also displayed significant clinical benefit in Phase
II clinical trials for the immunotherapy of HPV-related diseases. In the present study, we investigated 1) the
ability of HspE7 to prime E7-specific CD8+ T cells; 2) the ability of HspE7 to
induce CD8+ memory T cells; and 3) the in vivo efficacy of HspE7-induced
immunity in the protection of mice against murine tumor challenge.
Conclusions:
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HspE7 induces potent
E7-specific CTL
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Covalent linkage between Hsp65 and E7 is
required for efficient CTL induction
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CD8+ memory T cells primed by HspE7 are long
lived, persisting for at least 17 weeks
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HspE7-induced immunity confers protection against challenge with
E7-expressing murine tumor cells and the protection persists for at least 13
weeks
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This study provides greater
understanding of the mechanisms underlying the HspE7 therapeutic effects
observed in our clinical trials treating HPV-associated diseases.
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