Abstracts

Preliminary data from an open label study of HspE7 treatment of anal HSIL

Abstract presented at the 5th AIDS Malignancy Conference - Bethesda, Maryland, USA Æ April 23-25, 2001

Palefsky J.M.(1); Goldstone S.E.(2); 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 after the first injection (mo.). Each pt. was scored by the investigator on an analog scale for clinical improvement, taking into account all available information (Global Physician's Assessment, GPA). HPV was typed by PCR analysis of anal swabs. We report the first 22 consecutive pts. treated in this ongoing trial. results: 6/22 (27%) had downgraded to LSIL or better at 3 months. At 6 mo. 16/22 (73%) pts. downgraded to LSIL. There were no concurrent controls, but all responders had biopsy-proven persistent HSIL during at least 3 mo. before 9902. 21/21 (100%) pts. evaluated with GPA were improved and the mean score at 6 months was 88 (range 74-99), where no improvement from baseline is 50 and maximum possible improvement is 100. No serious adverse events were related to HspE7. 2/17 pts. and 1/15 responders were HPV16+. 10 HPV16- responders were positive for one or more other HPV types such as 6, 11, 18, 33, 40, 53 & 70.

Conclusions:
Pathological data suggest that HspE7 (500 mcg x3) will convert many pts. from HSIL to LSIL. Most downgrades occur between 3 and 6 mo. after the beginning of treatment. Almost all patients are assessed as clinically improved by the investigator (GPA). Response is not HPV16-specific. Treatment is well tolerated. Pts. continue to be followed.