A phase II study of Hsp-7 (SGN-00101) in women with high-grade cervical intraepithelial neoplasia

Objective. Approximately 2 million women worldwide are infected with high-risk human papillonnaviruses (HPV), resulting in a substantial risk for the development of invasive lower genital malignancies. This study was undertaken to determine the effects of vaccination with a protein encoding a bacteria] heat shock protein fused to sequences from the oncogenic E7 protein of HPV-16 in women with high-grade cervical intraepithelial neoplasia. Endpoints included lesion regression, immune response, and viral clearance. Methods. Twenty-one women were prospectively entered into an IRB-approved Phase 11 study. All women had biopsy-proven high-grade cervical intraepithelial neoplasia and persistent post-biopsy lesions visible by colposcopy. Four injections of HPV-16 Hsp E7 fusion protein at a dose of 500 mu g were given 3 weeks apart after which Loop Electrosurgical Excision of the Transformation Zone (LLETZ) was performed. Immune parameters were evaluated pre-vaccine and at the time of LLETZ, and HPV testing was performed at intervals before and after LLETZ. Study subjects were followed for 1 year after LLETZ. Results. Seven of 20 women (35%) evaluable for response had complete regression of their intraepithelial neoplasia at the time of LLETZ, I (5%) had regression to CIN I, II (55%) had stable disease and 1 (5%) had progression due to enlargement of her lesion. Immune responses were seen in 9 of the 17 women tested; 5 of the 7 complete responders had an immune response. Only 5 of 21 women had HPV-16 or -18. HPV clearance was not associated with lesion regression. Conclusion. Hsp-7 (SGN-00101), at this dose and schedule induced lesion regression in women with high-grade intraepithelial neoplasia. The fact that regression was correlated with immune response suggests that enhancing the immunogenicity of this vaccine may lead to improvement in the rate of lesion eradication. (c) 2007 Elsevier Inc. All rights reserved.