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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 Cancer¹

Frauenklinik, Friedrich-Schiller-University of Jena, 07743 Jena, Germany [A. M. K., A. S.]; Paterson Institute for Cancer Research, Christie Hospital, Manchester, England, United Kingdom [P. L. S., T. S. O., S. N. S.]; Ninewells Hospital and Medical School, Department of Cancer Medicine, University of Dundee, Scotland, United Kingdom [E. M. R.]; Frauenklinik, Klinikum Innenstadt, Ludwig-Maximilians-University, Munich, Germany [H. S., V. N.]; Velindre Hospital, Cardiff, Wales, United Kingdom [M. A.]; Department of Obstetrics and Gynaecology, St Mary’s Hospital, Manchester, England, United Kingdom [T. S. O., H. C. K.]; Frauenklinik, University of Bonn, Bonn, Germany [T. B.]; Frauenklinik, University of Tübingen, Tübingen, Germany [U. W.]; EORTC New Drug Development Office Oncology, Amsterdam, the Netherlands [K. K., J. W.]; Xenova Research Limited, Cambridge, England, United Kingdom [J. H., C. M. B., J. G., J. S. C. R.]; and University Clinic, Innsbruck, Austria [H. Z.]

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.

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