Induction of cytotoxic T lymphocytes with dendritic cells transfected withhuman papillomavirus E6 and E7 RNA: Implications for cervical cancer immunotherapy

Human papillomavirus (HPV) infection is associated with cervical cancer. Th e high-risk HPV E6 and E7 oncoproteins are constitutively expressed in most cervical carcinoma cells, and are, therefore, attractive antigens for cyto toxic T-lymphocyte (CTL)-mediated immunotherapy. The objective of this stud y was to evaluate the use of dendritic cells (DCs) transfected with RNA enc oding the E6 and E7 protein for cervical cancer immunotherapy. The authors have shown that DCs transfected with RNA-encoding antigen stimulate potent antigen-specific CTL responses in vitro and in vivo. In this study. they tr ied to determine whether DCs transfected with E6 and E7 RNA stimulate prima ry, antigen-specific CTL responses in vitro. The results show that DCs puls ed with E6 or E7 RNA stimulate antigen-specific CTL responses that recogniz e and lyse DCs transfected with E6 and E7 RNA and human cervical carcinoma cells expressing the E6 and E7 products, and the lysis was comparable to th at achieved with E6 and E7 peptide-pulsed DCs. Dendritic cells cotransfecte d with both E6 and E7 RNA stimulate CTLs that are more effective at lysing human cervical cancer cells. This study provides a rationale for the develo pment of cervical carcinoma immunotherapy using DCs transfected with HPV E6 and E7 RNA.