Recombinant Lipidated HPV E7 Induces a Th-1-Biased Immune Response and Protective Immunity against Cervical Cancer in a Mouse Model

摘要

The E7 oncoprotein of human papillomavirus (HPV) is an ideal target for developing immunotherapeutic strategies againstHPV-associated tumors. However, because protein-based immunogens alone are poor elicitors of the cytotoxic Tlymphocyte(CTL) responses, they have been difficult to exploit for therapeutic purposes. In this study, we report thata recombinant lipoprotein consisting of inactive E7 (E7m) biologically linked to a bacterial lipid moiety (rlipo-E7m) inducesthe maturation of mouse bone marrow-derived dendritic cells through toll-like receptor 2 (TLR2), skews the immuneresponses toward the Th1 responses and induces E7-specific CTL responses. We further studied the ability of rlipo-E7m toprovide protection against a TC-1 tumor cell challenge in an animal model. Mice prophylactically immunized with two 10-mgdoses of rlipo-E7m were found to be free of TC-1 tumor growth. Experiments in a therapeutic immunization model showedthat the tumor volume in mice receiving a single dose of rlipo-E7m was less than 0.01 cm3 on day 40, whereas the tumorvolume in mice treated with rE7m was 2.2861.21 cm3. The tumor volume of the entire control group was over 3 cm3. Inaddition, we demonstrated that the CD8+ T cells play a major role in anti-tumor immunity when administration of rlipo-E7m. These results demonstrate that rlipo-E7m could be a promising candidate for treating HPV-associated tumors.