Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82464
Title:
Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer.
Authors:
Kaufmann, Andreas M; Stern, Peter L; Rankin, Elaine M; Sommer, Harald; Nuessler, Volkmar; Schneider, Achim; Adams, Malcolm; Onon, Toli S; Bauknecht, Thomas; Wagner, Uwe; Kroon, Karlijn; Hickling, Julian K; Boswell, Christopher M; Stacey, Simon N; Kitchener, Henry C; Gillard, Jennifer; Wanders, Jantien; Roberts, John St C; Zwierzina, Heinz
Abstract:
PURPOSE: Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). HPV-16 or -18 is commonly present in 70% of cervical cancers. HPV-positive tumor cells present antigens of the viral protein in the context of human leukocyte antigen (HLA) class I that can be recognized by CTLs. We have conducted a study in patients with early-stage cervical cancer to assess the safety and immunological effects of vaccination with TA-HPV, a live recombinant vaccinia virus expressing modified forms of the HPV-16 and -18 E6 and E7 proteins. EXPERIMENTAL DESIGN: Twenty-nine patients with clinical International Federation of Gynecologists and Obstetricians (FIGO) stage Ib or IIa cervical cancer were given two vaccinations with TA-HPV at least 4 weeks apart, starting 2 weeks before radical hysterectomy. Patients were monitored closely for side effects of the vaccination. Serial blood samples were examined for HPV-specific CTLs or changes in levels of antibodies to HPV-16 or -18 E6 and E7 proteins and to vaccinia virus. RESULTS: Vaccination with recombinant vaccinia was well tolerated in all patients with only mild to moderate local toxicity, and no serious adverse events were attributable to the vaccine. After a single vaccination, HPV-specific CTLs were found in four patients (HLA A1, A3, three patients; HLA A1, A24, one patient). Eight patients developed HPV-specific serological responses. CONCLUSIONS: This study confirmed the safety and immunogenicity of the vaccine in a proportion of those patients vaccinated. Additional clinical studies using TA-HPV in combination with an additional experimental vaccine for HPV-16 are currently under way.
Affiliation:
Frauenklinik, Friedrich-Schiller-University of Jena, 07743 Jena, Germany. a.kaufmann@med.uni-jena.de
Citation:
Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer. 2002, 8 (12):3676-85 Clin. Cancer Res.
Journal:
Clinical Cancer Research
Issue Date:
Dec-2002
URI:
http://hdl.handle.net/10541/82464
PubMed ID:
12473576
Type:
Article
Language:
en
ISSN:
1078-0432
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKaufmann, Andreas M-
dc.contributor.authorStern, Peter L-
dc.contributor.authorRankin, Elaine M-
dc.contributor.authorSommer, Harald-
dc.contributor.authorNuessler, Volkmar-
dc.contributor.authorSchneider, Achim-
dc.contributor.authorAdams, Malcolm-
dc.contributor.authorOnon, Toli S-
dc.contributor.authorBauknecht, Thomas-
dc.contributor.authorWagner, Uwe-
dc.contributor.authorKroon, Karlijn-
dc.contributor.authorHickling, Julian K-
dc.contributor.authorBoswell, Christopher M-
dc.contributor.authorStacey, Simon N-
dc.contributor.authorKitchener, Henry C-
dc.contributor.authorGillard, Jennifer-
dc.contributor.authorWanders, Jantien-
dc.contributor.authorRoberts, John St C-
dc.contributor.authorZwierzina, Heinz-
dc.date.accessioned2009-09-24T10:15:37Z-
dc.date.available2009-09-24T10:15:37Z-
dc.date.issued2002-12-
dc.identifier.citationSafety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer. 2002, 8 (12):3676-85 Clin. Cancer Res.en
dc.identifier.issn1078-0432-
dc.identifier.pmid12473576-
dc.identifier.urihttp://hdl.handle.net/10541/82464-
dc.description.abstractPURPOSE: Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). HPV-16 or -18 is commonly present in 70% of cervical cancers. HPV-positive tumor cells present antigens of the viral protein in the context of human leukocyte antigen (HLA) class I that can be recognized by CTLs. We have conducted a study in patients with early-stage cervical cancer to assess the safety and immunological effects of vaccination with TA-HPV, a live recombinant vaccinia virus expressing modified forms of the HPV-16 and -18 E6 and E7 proteins. EXPERIMENTAL DESIGN: Twenty-nine patients with clinical International Federation of Gynecologists and Obstetricians (FIGO) stage Ib or IIa cervical cancer were given two vaccinations with TA-HPV at least 4 weeks apart, starting 2 weeks before radical hysterectomy. Patients were monitored closely for side effects of the vaccination. Serial blood samples were examined for HPV-specific CTLs or changes in levels of antibodies to HPV-16 or -18 E6 and E7 proteins and to vaccinia virus. RESULTS: Vaccination with recombinant vaccinia was well tolerated in all patients with only mild to moderate local toxicity, and no serious adverse events were attributable to the vaccine. After a single vaccination, HPV-specific CTLs were found in four patients (HLA A1, A3, three patients; HLA A1, A24, one patient). Eight patients developed HPV-specific serological responses. CONCLUSIONS: This study confirmed the safety and immunogenicity of the vaccine in a proportion of those patients vaccinated. Additional clinical studies using TA-HPV in combination with an additional experimental vaccine for HPV-16 are currently under way.en
dc.language.isoenen
dc.subjectCancer Stagingen
dc.subjectTumour Virus Infectionsen
dc.subjectUterine Cervical Canceren
dc.subject.meshAdenocarcinoma-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntibodies, Viral-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCervical Intraepithelial Neoplasia-
dc.subject.meshDNA, Viral-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFemale-
dc.subject.meshGenotype-
dc.subject.meshHLA-A1 Antigen-
dc.subject.meshHumans-
dc.subject.meshImmunoenzyme Techniques-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Staging-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshPapillomaviridae-
dc.subject.meshPapillomavirus Infections-
dc.subject.meshPapillomavirus Vaccines-
dc.subject.meshPhenotype-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshPolymorphism, Single-Stranded Conformational-
dc.subject.meshRepressor Proteins-
dc.subject.meshSeroepidemiologic Studies-
dc.subject.meshT-Lymphocytes, Cytotoxic-
dc.subject.meshTumor Virus Infections-
dc.subject.meshUterine Cervical Neoplasms-
dc.subject.meshVaccination-
dc.subject.meshVaccines, Synthetic-
dc.subject.meshVaccinia virus-
dc.subject.meshViral Vaccines-
dc.titleSafety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer.en
dc.typeArticleen
dc.contributor.departmentFrauenklinik, Friedrich-Schiller-University of Jena, 07743 Jena, Germany. a.kaufmann@med.uni-jena.deen
dc.identifier.journalClinical Cancer Researchen

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