Abstracts

15th Biennial Congress of the International Society for Sexually Transmitted Diseases Research (ISSTDR). "Stemming the Tide of STDs and HIV" July 27-30, 2003 The Ottawa Congress Centre

DETERMINATION OF IgG ANTIBODIES TO SGN-00101 (HspE7) IN SERA FROM PATIENTS WITH HPV- INDUCED DYSPLASIA TREATED WITH HspE7

 

Wiebe E², Boux, H¹, Winnett, M¹, Rowse, G², Neefe, J¹, and Siegel, M¹.

Stressgen Biotechnologies (¹ Collegeville, PA, USA, and ² Victoria, BC, Canada)

Objective:

Stressgen's immunization platform combines heat shock proteins (HSP) with protein antigens from viral or cancer targets into a single recombinant fusion protein. Pre-clinical data demonstrate the ability of Hsp fusion proteins to induce antigen-specific cytotoxic T lymphocytes, Type 1 cytokines and anti-tumor immunity. HspE7, a fusion of full length E7 antigen from Human Papilloma Virus (HPV) Type 16 onto full length Heat Shock Protein 65 from BCG (Hsp65), is in clinical development for treatment of diseases caused by HPV. HspE7 has shown activity in the treatment of anal intraepithelial neoplasia (AIN) and genital warts. The relationship of an HspE7 induced B-cell response to clinical outcome is unknown. This study reports the development of a dose and time dependent B cell response to the injection of HspE7 in patients with HPV induced AIN.

Methods:

Patients with high grade AIN received either placebo or 100 mcg HspE7 subcutaneously once a month for three months. Six months after the first dose, all patients received 500 mcg HspE7 once a month for three months. ELISA's were developed to determine total IgG against E7, Hsp65 and HspE7 in sera collected at various time points throughout the study.

Results:

Preexisting titers to all antigens were observed. Placebo treatment did not induce an increase in serum IgG anti-Hsp65, anti-HspE7 or anti-E7 antibodies. IgG anti-Hsp65 and anti-HspE7 antibody responses induced by HspE7 were robust; they were long lasting and of high titer. IgG anti-E7 antibody responses were also observed but were of lower overall titer. Antibody responses to all three antigens were boosted upon repeat dosing.

Conclusion:

Injection of HspE7 to patients with HPV induced disease induces IgG antibodies to the heat shock protein fusion and its component parts in a dose and time dependent manner.