Abstracts

Pathological response to treatment with HspE7 in anal dysplasia of multiple HPV types

Abstract presented at Cancer Vaccines 2000 - New York, NY, USA - October 2-4, 2000:

Palefsky J.M. (1); Goldstone S.E. (2); Boux L.J. (3); Neefe J.R. (3)

1) University of California, San Francisco, CA, USA,
2) Mt. Sinai School of Medicine, New York, NY, USA
3) Stressgen Biotechnologies, Inc., Collegeville, PA, USA

Background:
Human papillomavirus (HPV) causes anogenital squamous intraepithelial lesions (SIL), warts and anogenital cancer. Since treatment of SIL to prevent cancer often requires extensive surgery, we tested a novel HPV-specific immunotherapy.

Methods:
We made HspE7, fusing heat shock protein Hsp65 from BCG to E7 protein from HPV16. Patients (pts.) with persistent high grade SIL (HSIL) after completing treatment in a placebo-controlled trial of low dose (100 mcg) HspE7 crossed to open label trial 9902 (HspE7 500 mcg monthly x3). Response was taken as the most severe diagnosis after high resolution anoscopy with cytology and biopsy at 0, 3 & 6 months (mo.). HPV was typed by PCR analysis of anal swab. We report the first 21 consecutive pts. in this ongoing trial. E7 epitopes predicted to bind to 33 HLA class I molecules were identified for HPV16; these sequences were then sought in E7 from genital warts types 6 & 11 and high risk type 18. Results: At 3 mo. 5/21 (24%) pts. downgraded to low grade SIL (LSIL) or no SIL. At 6 mo. 4/6 (67%) pts. downgraded to LSIL. There were no concurrent controls, but all responders had biopsy-proven persistent HSIL during 3 mo. before 9902. No severe adverse events were related to HspE7. 5/21 pts. and 2/5 responders were HPV16+. Two responders typed 6 & 54 and 6 & 70 with 70 being 18-related. HPV16 epitopes binding HLA with highest affinities are shared by HPV6 & 11 E7 for 24/33 HLA molecules tested and by HPV18 E7 for 16/33 HLA molecules.

Conclusions:
Early pathological data suggest that HspE7 (500 mcg x3) will convert many pts. from HSIL to LSIL. Response is not HPV16-specific. Epitope analysis predicts that lesions of most or all high risk HPV (16- & 18-related) and, also, genital wart types 6 & 11 may respond to HspE7.