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

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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-γ 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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Abbreviations

B-LCL :

B-lymphoblastoid cell line

CTL :

Cytotoxic T lymphocyte

DC :

Dendritic cell

IL :

Interleukin

IFN-γ :

Interferon gamma

GM-CSF :

Granulocyte/macrophage-colony stimulating factor

HPV :

Human papillomavirus

PBL :

Peripheral blood lymphocytes

PBS :

Phosphate-buffered saline

TIL :

Tumor infiltrating lymphocytes

TNF-α:

Tumor necrosis factor alpha

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Acknowledgements

This work was supported in part by grants SCHN 294/6–1 and SCHN 294/6–2 of the Deutsche Forschungsgemeinschaft and by grant FKZ 01 ZZ 0105 of the BMBF. We would like to thank the clinical staff of the gynecological department of the Friedrich-Schiller-University for constant support.

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Authors and Affiliations

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

    Alfonso Ferrara, Marion Nonn, Carola Schreckenberger, Matthias Dürst, Achim Schneider & Andreas M. Kaufmann

  2. Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, INF 242, 69120, Heidelberg, Germany

    Peter Sehr & Michael Pawlita

Authors
  1. Alfonso Ferrara
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  2. Marion Nonn
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  3. Peter Sehr
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  4. Carola Schreckenberger
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  5. Michael Pawlita
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  6. Matthias Dürst
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  7. Achim Schneider
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  8. Andreas M. Kaufmann
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Corresponding author

Correspondence to Andreas M. Kaufmann.

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A. Ferrara and M. Nonn contributed equally to this work

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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 129, 521–530 (2003). https://doi.org/10.1007/s00432-003-0463-5

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  • DOI: https://doi.org/10.1007/s00432-003-0463-5

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