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HPV16E7 tumor antigen modified by KDEL sequence induce specific cytotoxic T lymphocytes-dependent antitumor immunity
Journal of Dermatological Science, 07/27/09

Yin R et al. – In a study to design a new HPV16 therapeutic vaccine using an endoplasmic reticulum (ER) retrieval signal and study its ability to induce the specific cytotoxic T lymphocytes (CTL) activity in vitro and in vivo, it appears that the ER retrieval signal-mediated antigen delivery system may have important clinical application for cancer therapy, even virus infectious disease and autoimmune disease.

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 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.

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