Vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia
| Autor: | Peter J, Baldwin, Sjoerd H, van der Burg, Christopher M, Boswell, Rienk, Offringa, Julian K, Hickling, Jennifer, Dobson, John St Clair, Roberts, John A, Latimer, Robin P, Moseley, Nicholas, Coleman, Margaret A, Stanley, Jane C, Sterling |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Vaginal Neoplasms Adolescent Vulvar Neoplasms Papillomavirus E7 Proteins T-Lymphocytes Papillomavirus Infections Vaccinia virus Oncogene Proteins Viral Middle Aged Cancer Vaccines DNA-Binding Proteins Repressor Proteins HLA-A2 Antigen Humans Female Safety Papillomaviridae Carcinoma in Situ T-Lymphocytes Cytotoxic |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 9(14) |
| ISSN: | 1078-0432 |
| Popis: | Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia.Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18.The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of women showed some improvement with an average decrease in lesion size of 40%. All cases showed an increased IgG titer and T-cell response to the vaccinia virus. An IFN-gamma enzyme-linked immunospot assay using pooled 22-mer peptides spanning HPV-16 E6 and E7 showed an increased specific T-cell response after vaccination in 6 of the 10 cases available for testing. There was no increase in specific cytotoxic response to selected individual HLA class I-restricted HPV-16 E6/7 peptides.The results suggest that the vaccine may have an effect on HPV-positive vulval intraepithelial neoplasia/vaginal intraepithelial neoplasia and that additional studies are warranted to develop an effective therapeutic vaccine. |
| Databáze: | OpenAIRE |
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