Infection by high-risk HPV (human papillomavirus) is the primary cause of cervical cancer. Dendritic cell-based (DC-based) therapeutic vaccine represents a promising approach to the prevention and treatment of many cancers, including HPV-related cancers, but current strategies have met with only limited success in preclinical and clinical research. It is necessary to find a properly and effective antigen presenting system of DC-based vaccine.
To design a new HPV16 therapeutic vaccine using an endoplasmic reticulum (ER) retrieval signal and study its ability to induce the specific CTL activity in vitro and in vivo.
E7(p)-KDEL and its control peptide were synthesized on solid phase. A series of methods were used, including standard 51Cr-labeled release assay, enzyme-linked immunospot (ELISPOT) assay and ELISA, to detect the CTL activity induced by different peptides. Prophylactic models and therapeutic models were examined to detect the in vivo effectiveness of E7(p)-KDEL-loaded DCs.
The specific CTL activity induced by E7(p)-KDEL-loaded DCs was much stronger than that induced by the other peptide-loaded DCs. Comparing with the control peptides, after incubation with the spleen cells of mice, the E7(p)-KDEL-loaded DCs could induce higher concentration of secreted IFN-γ and had higher ELISPOT numbers. In animal models, E7(p)-KDEL-loaded DCs vaccines effectively protected mice against fatal TC-1 tumor challenge and cured tumor-bearing mice.
The ER retrieval signal-mediated antigen delivery system may have important clinical application for cancer therapy, even virus infectious disease and autoimmune disease.
Abbreviations:HPV (human papillomavirus), KDEL (Lys-Asp-Glu-Leu), STDs (sexually transmitted diseases), SILs (squamous intraepithelial lesions), CTL (cytotoxic T lymphocyte), TCR (T cell receptor), APC (antigen presenting cells), DC (Dendritic cell), OVA (ovalbumin), HLA (human leucocyte antigen), TAP (Transporter associated with antigen processing), ELISPOT (enzyme-linked immunospot)
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Published online: July 12, 2010
Accepted: April 30, 2009
Received in revised form: April 22, 2009
Received: October 3, 2008
© 2009 Published by Elsevier Inc.