Recombinant human papillomavirus type 16 E7 protein as a model antigen to study the vaccine potential in control and E7 transgenic mice

Catherine M. Gérard, Nathalie Baudson, Kirsty Kraemer, Catherine Ledent, Andrew Mark Pardoll, Claudine Bruck

Research output: Contribution to journalArticle

Abstract

The early genes E6 and E7 of human papillomavirus type 16 (HPV16) are consistently and exclusively expressed in HPV16-induced cancer lesions and play major roles in the development and maintenance of the malignant phenotype. Because this protein is a good example of a tumor-associated antigen, we have used E7 as a model antigen to test the potential of an experimental vaccine as an immunotherapeutic approach. In this study, we used a murine E7-expressing tumor model (TC1 cells) to assess effects of an E7-based vaccine on tumor growth. We show that vaccination with the E7 protein, formulated in the SmithKline Beecham Biologicals proprietary adjuvants (SBAS 1 and SBAS 2), leads to the rejection of pre-established tumors. Tumor rejection was associated with the induction of a strong systemic T helper 1 response, including CTLs, and the presence of an inflammatory infiltrate within the regressing tumor. Because most identified tumor-associated antigens are self antigens rather viral antigens, we used E7 transgenic mice to evaluate the E7-based vaccine in conditions where E7 is a self antigen. Transgenic mice, which constitutively and specifically express the E7 HPV16 gene in the thyroid epithelium, rapidly develop thyroid goiters and, after several months, thyroid carcinomas. We show that E7-specific antibodies and CD4 T helper responses can be obtained by vaccinating E7 transgenic mice, although a CTL response was not detected. Despite the absence of measurable CTL responses, vaccination still reduced the growth of pre-established TC1 tumors, although less efficiently than in nontransgenic animals, but was unable to suppress or delay the development of the spontaneous thyroid pathology.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume7
Issue number11 SUPPL.
StatePublished - Mar 2001

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Papillomavirus E7 Proteins
Human papillomavirus 16
Transgenic Mice
Vaccines
Antigens
Neoplasms
Thyroid Gland
Autoantigens
Neoplasm Antigens
Vaccination
Cancer Vaccines
Viral Antigens
Goiter
Cytotoxic T-Lymphocytes
Growth
Thyroid Neoplasms
Genes
Proteins
Epithelium
Maintenance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Recombinant human papillomavirus type 16 E7 protein as a model antigen to study the vaccine potential in control and E7 transgenic mice. / Gérard, Catherine M.; Baudson, Nathalie; Kraemer, Kirsty; Ledent, Catherine; Pardoll, Andrew Mark; Bruck, Claudine.

In: Clinical Cancer Research, Vol. 7, No. 11 SUPPL., 03.2001.

Research output: Contribution to journalArticle

Gérard, Catherine M. ; Baudson, Nathalie ; Kraemer, Kirsty ; Ledent, Catherine ; Pardoll, Andrew Mark ; Bruck, Claudine. / Recombinant human papillomavirus type 16 E7 protein as a model antigen to study the vaccine potential in control and E7 transgenic mice. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 11 SUPPL.
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