Document Detail

Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III.
MedLine Citation:
PMID:  17586030     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: SGN-00101 (HspE7, Nventa, San Diego, CA) is a novel therapeutic vaccine consisting of a fusion protein containing an M. bovis BCG heat shock protein (Hsp65) covalently linked to the entire sequence of HPV 16 E7. This trial was designed to evaluate the efficacy and toxicities of HspE7 in women with CIN III.
METHODS: HIV (-) women with biopsy-proven CIN III were eligible. Two cohorts were accrued; one cohort to establish efficacy and a second cohort with a longer follow-up period to improve the precision of the trial to estimate response rates. Each patient underwent 3 monthly subcutaneous vaccinations with 500 microg of HspE7 followed by monthly colposcopic follow-up for 1 month in cohort 1 and an extended observation period (2 months) in cohort 2. All patients then underwent a LEEP or cone biopsy of the cervix. A complete pathologic response (pCR) was defined as no evidence of CIN or CIN I (only HPV changes). A partial response (PR) was defined as colposcopic lesion regression of >50% in size. Cervicovaginal lavage samples were obtained at each visit for HPV typing using MY09/ MY11 HPV PCR.
RESULTS: Seventy-two patients were registered and screened, of whom 64 were eligible. Fifty-eight patients completed the trial and were evaluable (31 in cohort 1, 27 in cohort 2). There were no significant epidemiologic or HPV type differences between the 2 cohorts so responses were combined for analysis. Of the 58 evaluable patients, 13 (22.5%) had a pCR; 32 (55%) had a PR and 11 (19%) had stable disease. Two (3.5%) patients in cohort 2 had microinvasive disease and were defined as progressive disease. Thirty-three of 58 (57%) of the patients were infected with HPV 16 prior to vaccination or in subsequent visits. There was no significant difference in regression in women infected with HPV 16 compared to those without HPV 16 infection (88% vs. 70%; p=0.12). Women who had a previous LEEP or ablation for CIN were 2.7 times more likely to have a complete response compared to patients without previous treatment, although the difference was not statistically significant (95% CI for rate ratio: 0.95-6.19, p=0.10). At a cellular level, there was a significant association between local inflammation and response; lower grade of lesional inflammation correlated with a response to HspE7 (p=0.04 using Wilcoxon rank sum test).
CONCLUSIONS: HspE7 appeared to demonstrate activity in women with CIN III and met a priori assumptions for efficacy; however, it is unclear whether this response was due to natural regression rather than treatment effect. HspE7, which targets the HPV 16 E7 oncoprotein, had efficacy in patients infected with HPV types other than 16, suggesting cross-reactivity. A larger randomized, controlled trial is needed to better define efficacy and to identify subsets of women most likely to benefit from immunotherapy.
Mark H Einstein; Anna S Kadish; Robert D Burk; Mimi Y Kim; Scott Wadler; Howard Streicher; Gary L Goldberg; Carolyn D Runowicz
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-22
Journal Detail:
Title:  Gynecologic oncology     Volume:  106     ISSN:  0090-8258     ISO Abbreviation:  Gynecol. Oncol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-31     Completed Date:  2007-10-11     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  453-60     Citation Subset:  IM    
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MeSH Terms
Bacterial Proteins / immunology
Cancer Vaccines / adverse effects,  therapeutic use*
Cervical Intraepithelial Neoplasia / therapy*
Chaperonin 60
Chaperonins / immunology
Cohort Studies
Oncogene Proteins, Viral / immunology
Papillomavirus E7 Proteins
Recombinant Fusion Proteins / immunology
Uterine Cervical Neoplasms / therapy*
Grant Support
AI-51519/AI/NIAID NIH HHS; K12 RR017672/RR/NCRR NIH HHS; K12 RR017672/RR/NCRR NIH HHS; K12 RR017672-01/RR/NCRR NIH HHS; L30 CA110417/CA/NCI NIH HHS; L30 CA110417-01/CA/NCI NIH HHS; N01 CM17103/CM/NCI NIH HHS; P30 AI051519/AI/NIAID NIH HHS; P30 AI051519-01A1/AI/NIAID NIH HHS; P30 AI051519-01A19001/AI/NIAID NIH HHS; P30 AI051519-03/AI/NIAID NIH HHS; R01 CA148966/CA/NCI NIH HHS; U01 CA063422-04/CA/NCI NIH HHS; U01 CA063422-04S4/CA/NCI NIH HHS
Reg. No./Substance:
0/Bacterial Proteins; 0/Cancer Vaccines; 0/Chaperonin 60; 0/Oncogene Proteins, Viral; 0/Papillomavirus E7 Proteins; 0/Recombinant Fusion Proteins; 0/heat-shock protein 65, Mycobacterium; 0/oncogene protein E7, Human papillomavirus type 16; EC 3.6.1.-/Chaperonins

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