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Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients.

Abstract

PURPOSE

Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancer. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded autologous dendritic cells (DC) were evaluated as cellular tumor vaccine in a case series of cervical cancer patients.

METHODS

Autologous monocyte-derived DCs were pulsed with recombinant HPV16 E7 or HPV18 E7 oncoprotein and administered to 15 stage IV cervical cancer patients. Safety, toxicity, and induction of serological and cellular immune responses were monitored.

RESULTS

The vaccine was well-tolerated and no local or systemic side effects or toxicity were recorded. A specific serologic response was seen in 3/11 evaluated patients. Specific cellular immune responses (4/11) were detected with 2/10 positive de novo reactions plus one boosted preexistent response in proliferation assays and 3/11 in IFN-gamma ELISpot assays. A transient drop in tumor marker SCC was observed in 5/9 evaluable patients but did not correlate with markers of the immune response. No objective clinical response was observed. Tumor biopsies available from four patients showed severe or complete loss of HLA expression in three of the advanced tumors.

CONCLUSION

Autologous dendritic cells pulsed with HPV E7 protein can induce T cell responses in a portion of late stage cervical cancer patients. Boosting of immune responses by adjuvants and vaccination of tumor HLA-positive patients will be mandatory in future trials.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Gynäkologische Molekularbiologie, Universitätsfrauenklinik, Friedrich-Schiller-Universität Jena, Bachstrasse 18, 07743, Jena, Germany.

    , , , , , ,

    Source

    MeSH

    Adult
    Cancer Vaccines
    Cell Division
    Dendritic Cells
    Enzyme-Linked Immunosorbent Assay
    Female
    HLA-A Antigens
    Humans
    Interferon-gamma
    Middle Aged
    Neoplasm Staging
    Oncogene Proteins, Viral
    Papillomavirus E7 Proteins
    Pilot Projects
    Time Factors
    Uterine Cervical Neoplasms

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    12898233

    Citation

    Ferrara, Alfonso, et al. "Dendritic Cell-based Tumor Vaccine for Cervical Cancer II: Results of a Clinical Pilot Study in 15 Individual Patients." Journal of Cancer Research and Clinical Oncology, vol. 129, no. 9, 2003, pp. 521-30.
    Ferrara A, Nonn M, Sehr P, et al. Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients. J Cancer Res Clin Oncol. 2003;129(9):521-30.
    Ferrara, A., Nonn, M., Sehr, P., Schreckenberger, C., Pawlita, M., Dürst, M., ... Kaufmann, A. M. (2003). Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients. Journal of Cancer Research and Clinical Oncology, 129(9), pp. 521-30.
    Ferrara A, et al. Dendritic Cell-based Tumor Vaccine for Cervical Cancer II: Results of a Clinical Pilot Study in 15 Individual Patients. J Cancer Res Clin Oncol. 2003;129(9):521-30. PubMed PMID: 12898233.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients. AU - Ferrara,Alfonso, AU - Nonn,Marion, AU - Sehr,Peter, AU - Schreckenberger,Carola, AU - Pawlita,Michael, AU - Dürst,Matthias, AU - Schneider,Achim, AU - Kaufmann,Andreas M, Y1 - 2003/07/30/ PY - 2002/10/21/received PY - 2003/05/09/accepted PY - 2003/8/5/pubmed PY - 2003/12/3/medline PY - 2003/8/5/entrez SP - 521 EP - 30 JF - Journal of cancer research and clinical oncology JO - J. Cancer Res. Clin. Oncol. VL - 129 IS - 9 N2 - PURPOSE: Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancer. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded autologous dendritic cells (DC) were evaluated as cellular tumor vaccine in a case series of cervical cancer patients. METHODS: Autologous monocyte-derived DCs were pulsed with recombinant HPV16 E7 or HPV18 E7 oncoprotein and administered to 15 stage IV cervical cancer patients. Safety, toxicity, and induction of serological and cellular immune responses were monitored. RESULTS: The vaccine was well-tolerated and no local or systemic side effects or toxicity were recorded. A specific serologic response was seen in 3/11 evaluated patients. Specific cellular immune responses (4/11) were detected with 2/10 positive de novo reactions plus one boosted preexistent response in proliferation assays and 3/11 in IFN-gamma ELISpot assays. A transient drop in tumor marker SCC was observed in 5/9 evaluable patients but did not correlate with markers of the immune response. No objective clinical response was observed. Tumor biopsies available from four patients showed severe or complete loss of HLA expression in three of the advanced tumors. CONCLUSION: Autologous dendritic cells pulsed with HPV E7 protein can induce T cell responses in a portion of late stage cervical cancer patients. Boosting of immune responses by adjuvants and vaccination of tumor HLA-positive patients will be mandatory in future trials. SN - 0171-5216 UR - https://wwww.unboundmedicine.com/medline/citation/12898233/Dendritic_cell_based_tumor_vaccine_for_cervical_cancer_II:_results_of_a_clinical_pilot_study_in_15_individual_patients_ L2 - https://dx.doi.org/10.1007/s00432-003-0463-5 DB - PRIME DP - Unbound Medicine ER -