Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Michael A. Steller, Karen J. Gurski, Masaru Murakami, Richard W. Daniel, Keerti V. Shah, Esteban Celis, Alessandro Sette, Edward L. Trimble, Robert C. Park, Francesco M. Marincola

Research output: Contribution to journalArticle

169 Scopus citations

Abstract

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitopespecific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-γ release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.

Original languageEnglish (US)
Pages (from-to)2103-2109
Number of pages7
JournalClinical Cancer Research
Volume4
Issue number9
StatePublished - Sep 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Steller, M. A., Gurski, K. J., Murakami, M., Daniel, R. W., Shah, K. V., Celis, E., Sette, A., Trimble, E. L., Park, R. C., & Marincola, F. M. (1998). Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7. Clinical Cancer Research, 4(9), 2103-2109.