Abstract
Background
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.
Objective
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.
Methods
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.
Results
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.
Conclusions
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)Keywords
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Article info
Publication history
Published online: July 12, 2010
Accepted:
April 30,
2009
Received in revised form:
April 22,
2009
Received:
October 3,
2008
Identification
Copyright
© 2009 Published by Elsevier Inc.
