Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia.

ABSTRACT: PURPOSE:Infection with oncogenic human papillomaviruses has been linked to the development of cervical neoplasia and cancer. The exclusive expression of E7, a viral oncogene, in infected cells makes this protein an ideal target for immunotherapy. We recently reported on the results of a trial in women with cervical carcinoma-in-situ using HspE7, a protein vaccine consisting of full length HPV16 E7 linked to a heat shock protein from M. bovis. The stimulating effects of HspE7 on specific cytotoxic T lymphocytes have been demonstrated in vitro and in (pre-)clinical trials. The induction of a B-cell response by HspE7 and its association with clinical outcome is unknown, and is the purpose of this study. EXPERIMENTAL DESIGN:We measured the serum IgG levels against HPV16 E7 and HPV16 and -18 VLPs using a multiplexed Luminex based assay in 57 women with CIS who received the HspE7 vaccine. RESULTS:Vaccination with HspE7 results in a modest, yet maintained increase in HPV16 E7 specific IgG levels. While not significant, increased HPV16 E7 IgG levels appear to be correlated with a positive therapeutic effect. Women who were previously treated for recurrent disease (by LEEP) had significantly higher HPV16 E7 IgG levels compared with subjects without recurrent disease (p=0.01). In women with recurrent disease, higher IgG levels correlated with complete pathological response. CONCLUSIONS:This study suggests that IgG levels could potentially be used as a marker for response to a therapeutic vaccine. Further translational investigations of the 'priming' of local immune responses using extirpative procedures should be explored.

SUBMITTER: Van Doorslaer K 

PROVIDER: S-EPMC2813920 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature