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


CONCLUSIONS
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.
Ferrara
Alfonso
A
Gynäkologische Molekularbiologie, Universitätsfrauenklinik, Friedrich-Schiller-Universität Jena, Bachstrasse 18, 07743, Jena, Germany.
Nonn
Marion
M
Sehr
Peter
P
Schreckenberger
Carola
C
Pawlita
Michael
M
Dürst
Matthias
M
Schneider
Achim
A
Kaufmann
Andreas M
AM
D000328:Adult; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D010865:Pilot Projects; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*
D019496:Cancer Vaccines; D015234:HLA-A Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma