Dendritic cell-based tumor vaccine for cervical cancer I: in vitro stimulation with recombinant protein-pulsed dendritic cells induces specific T cells to HPV16 E7 or HPV18 E7.

Abstract:

PURPOSE:Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancers. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded dendritic cells (DC) were evaluated as cellular tumor vaccine. METHODS:Autologous monocyte-derived DCs loaded with recombinant HPV16 or HPV18 E7 oncoprotein were used to induce in vitro a specific T cell response. Specificities of activated T cells were determined. RESULTS:E7-specific T cells could be identified in 18/20 T cell lines from healthy blood donors. CD4(+) T cell responses (13/16) were found by proliferation assay. CD8(+) CTLs (12/18) were detectable by interferon-gamma (IFN-gamma) ELISpot analysis. Seven donors reacted in both assays and only 2/20 T cell lines did not react in any assay. Thus, specific T cells could be activated in >80% of healthy individuals. T cell lines from suitable donors were specific for HLA-A*0201-restricted epitopes. Furthermore, HPV E7 antigen-loaded DC stimulated specific responses in freshly isolated tumor infiltrating lymphocyte (TIL) populations of cervical cancer patients. CONCLUSION:Autologous dendritic cells loaded with HPV E7 protein can induce T cell responses in healthy individuals by in vitro stimulation and evoke responses in TIL from cervical cancer biopsies. Since there are no limitations with respect to specific HLA-haplotypes, these findings may be a basis for the development of a therapeutic protein-based DC tumor vaccine against cervical cancer for HPV16- and HPV18-positive patients.

authors

Nonn M,Schinz M,Zumbach K,Pawlita M,Schneider A,Dürst M,Kaufmann AM

doi

10.1007/s00432-003-0462-6

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

511-20

issue

9

eissn

0171-5216

issn

1432-1335

journal_volume

129

pub_type

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