Abstracts

HLA-A2 and H-2Db-restricted CTL activity induced by SGN-00101 - a fusion protein comprised of heat shock protein and human papillomavirus E7

Abstract presented at 5th Annual Conference on Vaccine Research - Baltimore, MD, USA - May 6-8, 2002

Liu H.; Rowse G.; Chu N.R.; Wu B.; Boux H.; and Siegel M.I. (2)

Stressgen Biotechnologies Corporation, Victoria, BC, Canada
2) Stressgen Biotechnologies, Inc., Collegeville, PA, USA

Infection with human papillomavirus type 16 (HPV16) is strongly associated with cervical carcinogenesis. It is believed that induction of T cell-mediated immunity, particularly cytolytic T lymphocytes (CTL), is important in 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 cell line (TC-1) can be prevented by treatment with SGN-00101, an Hsp fusion protein comprised of Mycobacterium bovis BCG Hsp65 linked to HPV16 E7. In the present study, we investigated the ability of SGN-00101 to prime E7-specific CTL activity. Splenocytes from mice immunized with SGN-00101 were restimulated in vitro with HPV16 E7-derived CTL epitope peptides. CTL activities were measured using 51Cr-labeled peptide-pulsed or E7-expressing target cells. Results indicated that SGN-00101 was effective in priming HLA-A2-restricted CTL in A2.1/Kb transgenic mice and H-2Db-restricted CTL in C57BL/6 mice. In addition to lysing target cells pulsed with peptides, the E7 specific CTL were capable of lysing target cells expressing E7 endogenously. Significant CTL activity was observed (60% at 100:1 E:T ratio) in both mouse strains. The present study supports the previous findings that Hsp fusion proteins are capable of inducing peptide-specific CTL activity. This study provides additional support for the use of SGN-00101 to treat HPV-related disease.