Detection of t helper responses, but not of human papillomavirus-specific cytotoxic t lymphocyte responses, after peptide vaccination of patients with cervical carcinoma

Maaike E. Ressing, Willemien J. van Driel, Remco M.P. Brandt, Gemma G. Kenter, Joan H. de Jong, Thomas Bauknecht, Gert Jan Fleuren, Peter Hoogerhout, Rienk Offringa, Alessandro Sette, Esteban Celis, Howard Grey, Baptist J. Trimbos, W. Martin Kast, Cornelis J.M. Melief

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Human papillomavirus type 16 (HPV16)-encoded E7 oncoprotein is constitutively expressed in cervical carcinoma cells and is required for cellular transformation to be maintained. The E7 protein, therefore, forms an attractive target for T-cell-mediated immune intervention to prevent or treat HPV16+tumors. The authors performed a peptide-based phase I/II vaccination trial to induce anti-tumor immune responses in patients with recurrent or residual cervical carcinoma. Fifteen HLA-A*0201+patients with HPV16+cervical carcinoma received vaccinations with synthetic peptides representing 2 HPV16 E7-encoded, HLA-A*0201-restricted cytotoxic T lymphocyte epitopes and a pan-HLA-DR-binding T-helper epitope, PADRE, in adjuvant. No signs of toxicity were observed. Two patients had stable disease for more than 1 year after vaccination, 3 patients died of the disease during or shortly after the vaccination period, and 10 patients maintained progressive cervical carcinoma. Specific immune responses directed against the vaccine components were analyzed in peripheral blood samples. No cytotoxic T lymphocyte responses against the HPV16 E7 peptides were detectable. After vaccination, strong PADRE helper peptide-specific proliferation was detected in 4 of 12 patients. In conclusion, peptide vaccination with 2 HPV16 E7 cytotoxic T lymphocyte epitopes and a universal T helper epitope is well tolerated by patients with advanced cervical carcinoma. Despite a reduction of in vitro cytolytic or proliferative recall responses to some, but not all, conventional antigens in this patient group, peptide-specific proliferative responses were induced in 4 patients. Based on the current study, it is now feasible to perform peptide vaccination in earlier stages of HPV16-induced cervical disease.

Original languageEnglish (US)
Pages (from-to)255-266
Number of pages12
JournalJournal of Immunotherapy
Volume23
Issue number2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Human papillomavirus 16
Vaccination
Lymphocytes
Carcinoma
Peptides
Cytotoxic T-Lymphocytes
T-Lymphocyte Epitopes
Epitopes
Oncogene Proteins
HLA-DR Antigens
Neoplasms
Vaccines
T-Lymphocytes
Antigens

Keywords

  • Cervical carcinoma
  • Human papillomavirus
  • Immunocompetence
  • Peptide
  • Vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Detection of t helper responses, but not of human papillomavirus-specific cytotoxic t lymphocyte responses, after peptide vaccination of patients with cervical carcinoma. / Ressing, Maaike E.; van Driel, Willemien J.; Brandt, Remco M.P.; Kenter, Gemma G.; de Jong, Joan H.; Bauknecht, Thomas; Fleuren, Gert Jan; Hoogerhout, Peter; Offringa, Rienk; Sette, Alessandro; Celis, Esteban; Grey, Howard; Trimbos, Baptist J.; Kast, W. Martin; Melief, Cornelis J.M.

In: Journal of Immunotherapy, Vol. 23, No. 2, 01.01.2000, p. 255-266.

Research output: Contribution to journalArticle

Ressing, ME, van Driel, WJ, Brandt, RMP, Kenter, GG, de Jong, JH, Bauknecht, T, Fleuren, GJ, Hoogerhout, P, Offringa, R, Sette, A, Celis, E, Grey, H, Trimbos, BJ, Kast, WM & Melief, CJM 2000, 'Detection of t helper responses, but not of human papillomavirus-specific cytotoxic t lymphocyte responses, after peptide vaccination of patients with cervical carcinoma', Journal of Immunotherapy, vol. 23, no. 2, pp. 255-266. https://doi.org/10.1097/00002371-200003000-00010
Ressing, Maaike E. ; van Driel, Willemien J. ; Brandt, Remco M.P. ; Kenter, Gemma G. ; de Jong, Joan H. ; Bauknecht, Thomas ; Fleuren, Gert Jan ; Hoogerhout, Peter ; Offringa, Rienk ; Sette, Alessandro ; Celis, Esteban ; Grey, Howard ; Trimbos, Baptist J. ; Kast, W. Martin ; Melief, Cornelis J.M. / Detection of t helper responses, but not of human papillomavirus-specific cytotoxic t lymphocyte responses, after peptide vaccination of patients with cervical carcinoma. In: Journal of Immunotherapy. 2000 ; Vol. 23, No. 2. pp. 255-266.
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abstract = "Human papillomavirus type 16 (HPV16)-encoded E7 oncoprotein is constitutively expressed in cervical carcinoma cells and is required for cellular transformation to be maintained. The E7 protein, therefore, forms an attractive target for T-cell-mediated immune intervention to prevent or treat HPV16+tumors. The authors performed a peptide-based phase I/II vaccination trial to induce anti-tumor immune responses in patients with recurrent or residual cervical carcinoma. Fifteen HLA-A*0201+patients with HPV16+cervical carcinoma received vaccinations with synthetic peptides representing 2 HPV16 E7-encoded, HLA-A*0201-restricted cytotoxic T lymphocyte epitopes and a pan-HLA-DR-binding T-helper epitope, PADRE, in adjuvant. No signs of toxicity were observed. Two patients had stable disease for more than 1 year after vaccination, 3 patients died of the disease during or shortly after the vaccination period, and 10 patients maintained progressive cervical carcinoma. Specific immune responses directed against the vaccine components were analyzed in peripheral blood samples. No cytotoxic T lymphocyte responses against the HPV16 E7 peptides were detectable. After vaccination, strong PADRE helper peptide-specific proliferation was detected in 4 of 12 patients. In conclusion, peptide vaccination with 2 HPV16 E7 cytotoxic T lymphocyte epitopes and a universal T helper epitope is well tolerated by patients with advanced cervical carcinoma. Despite a reduction of in vitro cytolytic or proliferative recall responses to some, but not all, conventional antigens in this patient group, peptide-specific proliferative responses were induced in 4 patients. Based on the current study, it is now feasible to perform peptide vaccination in earlier stages of HPV16-induced cervical disease.",
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AU - Kenter, Gemma G.

AU - de Jong, Joan H.

AU - Bauknecht, Thomas

AU - Fleuren, Gert Jan

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AU - Offringa, Rienk

AU - Sette, Alessandro

AU - Celis, Esteban

AU - Grey, Howard

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N2 - Human papillomavirus type 16 (HPV16)-encoded E7 oncoprotein is constitutively expressed in cervical carcinoma cells and is required for cellular transformation to be maintained. The E7 protein, therefore, forms an attractive target for T-cell-mediated immune intervention to prevent or treat HPV16+tumors. The authors performed a peptide-based phase I/II vaccination trial to induce anti-tumor immune responses in patients with recurrent or residual cervical carcinoma. Fifteen HLA-A*0201+patients with HPV16+cervical carcinoma received vaccinations with synthetic peptides representing 2 HPV16 E7-encoded, HLA-A*0201-restricted cytotoxic T lymphocyte epitopes and a pan-HLA-DR-binding T-helper epitope, PADRE, in adjuvant. No signs of toxicity were observed. Two patients had stable disease for more than 1 year after vaccination, 3 patients died of the disease during or shortly after the vaccination period, and 10 patients maintained progressive cervical carcinoma. Specific immune responses directed against the vaccine components were analyzed in peripheral blood samples. No cytotoxic T lymphocyte responses against the HPV16 E7 peptides were detectable. After vaccination, strong PADRE helper peptide-specific proliferation was detected in 4 of 12 patients. In conclusion, peptide vaccination with 2 HPV16 E7 cytotoxic T lymphocyte epitopes and a universal T helper epitope is well tolerated by patients with advanced cervical carcinoma. Despite a reduction of in vitro cytolytic or proliferative recall responses to some, but not all, conventional antigens in this patient group, peptide-specific proliferative responses were induced in 4 patients. Based on the current study, it is now feasible to perform peptide vaccination in earlier stages of HPV16-induced cervical disease.

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