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 papillomaviruses (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 bacterial 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 II 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 mug 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, 1 (5%) had regression to CIN I, 11 (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.


CONCLUSIONS
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.
Roman
L D
LD
Department of Obstetrics and Gynecology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA. lroman@hsc.usc.edu
Wilczynski
S
S
Muderspach
L I
LI
Burnett
A F
AF
O'Meara
A
A
Brinkman
J A
JA
Kast
W M
WM
Facio
G
G
Felix
J C
JC
Aldana
M
M
Weber
J S
JS
D000328:Adult; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology
D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C074119:heat-shock protein 65, Mycobacterium; C059731:oncogene protein E7, Human papillomavirus type 16; D018833:Chaperonins