Abstracts

Antigen-Specific Cell-Mediated Immunity in a Phase I Dose-Escalation Trial of Single Doses of HspE7 in Healthy Volunteers.

Abstract presented at American Society of Clinical Oncology 36th Annual Meeting - New Orleans, LA May 20-23, 2000 as published in 2000 American Society of Clinical Oncology Programs/Proceedings Volume 19 Abstract #1789

Kadish A.S.(1), Ho G.(1), Wang Y.(1), He W.(1), Chu N.R.(2), Winnett M.(3), Talluri K.(4), Mizzen L.(2), Siegel M.I.(3), Neefe J.R.(3)

1) Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
2) Stressgen Biotechnologies Corporation, Victoria, BC, Canada
3) Stressgen Biotechnologies, Inc., Collegeville, PA, USA
4) PPD Development, Morrisville, NC, USA.

Human papillomavirus (HPV) causes serious disease including cervical
dysplasia and cancer. We have constructed a fusion protein, HspE7,
consisting of the heat shock protein Hsp65 from M. bovis BCG linked to the Rb-binding E7 protein from the oncogenic HPV type 16. A randomized, double-blind, placebo-controlled trial of single subcutaneous doses of HspE7 was conducted in 24 healthy volunteers at a single site. Four cohorts of 6 patients were treated with a ratio of 2:1 active:placebo at doses of 10, 30, 100, and 500 mcg. No severe or serious adverse events were seen. The most common adverse event was mild to moderate local reaction at the injection site, resolving without treatment. Peripheral blood mononuclear cells, sampled before and at 2 and 4 weeks after treatment, were cultured for up to three weeks with in vitro stimulation by peptides from E7. Proliferative responses, an indicator of cell-mediated immunity (CMI), were measured as incorporation of tritiated thymidine. At 2 weeks after treatment, 33% of subjects treated at 10, 30 or 100 mcg converted from CMI negative to CMI positive for at least one of four E7 peptides tested. No placebo patient converted. Due to the small sample size, the differences among treatment groups were not statistically significant. At four weeks, the CMI responses among treatment groups were similar. Subjects receiving 500 mcg showed lower responses; this observation suggested altered kinetics of response, differences among the subjects in the various treatment groups, or a difference in the biologic effect of the higher dose. Some subjects displayed responses without active treatment; this observation suggests exposure to microorganisms carrying the relevant antigens. The data are consistent with the hypothesis that a single exposure of humans to HspE7, 10-100 mcg, results in transient expression of specific immunity in the peripheral blood of some patients. Further studies of detailed kinetics in a larger population and studies of multiple doses in this dose range are warranted.