In vitro and in vivo evaluations of human papillomavirus type 16 (HPV16)-derived peptide-loaded dendritic cells (DCs) with a CpG oligodeoxynucleotide (CpG-ODN) adjuvant as tumor vaccines for immunotherapy of cervical cancer.

PURPOSE

To evaluate the immunotherapeutic potentials for human dendritic cells (DCs) loaded with different HPV16-associated antigens, including HPV16E7 (E) protein, HPV16E7 polypeptide (P), as well as CpG-oligodeoxynucleotide (ODN) 2006 as a promising immune adjuvant for vaccination against cervical carcinoma.

METHODS

DCs derived from human peripheral blood and cord blood were isolated and loaded with HPV-derived protein or peptides, in combination with CpG-ODN2006 as a potential adjuvant. The IL-12 level, the allogeneic T cell-stimulatory capacity and the cytotoxicity of cytotoxic T lymphocytes (CTLs) were evaluated in vitro. Furthermore, an immune reconstitution model of human cervical carcinoma in SCID mice was used to assess the anti-tumor effects in vivo. The tumor sizes, the expression of IgG and IFN-γ, and the presence of the human CD3(+), CD4(+) and CD8(+) T cells were measured in the mice inoculated with different DCs.

RESULTS

The antigen-loaded DCs displayed obvious anti-tumor activities in vitro and in vivo, and showed no toxicity to normal cells. The level of IL-12, an important cytokine for immune response, was up-regulated in all mice inoculated with antigen-loaded DCs. Stimulation and activity of CTLs were increased after treatment with antigen-loaded DCs. Significantly, DCs loaded with HPV16E7 polypeptide (P) showed the most distinguished immunotherapeutic activities, and such effect was further enhanced when HPV16E7 polypeptide (P) was used in combination with CpG-ODN2006. Interestingly, the same results were obtained in vivo: the tumor size was decreased, and IgG and IFN-γ levels were increased after the SCID mice were inoculated with the loaded DCs.

CONCLUSIONS

HPV16E7 polypeptide combined with the immune adjuvant CpG-ODN2006 could be a suitable HPV16-associated tumor antigen. The research provides a new strategy for generating DCs vaccines for immunotherapy of cervical cancer.