Induction of anti-tumor immunity by dendritic cells pulsed with an endoplasmic reticulum retrieval signal modifies heparanase epitope in mice
ABSTRACT
BACKGROUND AIMS: It has been reported that the heparanase epitope can elicit a CTL-mediated anti-tumor response; however, the potential of the heparanase epitope modified by an endoplasmic reticulum (ER) retrieval signal, a C-terminal Lys-Asp-Glu-Leu sequence, is still unknown.
METHODS: The heparanase epitope was modified by ER retrieval signal, and dendritic cells (DC) were pulsed with the modified peptide. The location and presentation of the modified peptide were detected, and the potential of the anti-tumor response was assessed.
RESULTS: The modified peptide could target the ER of DC to form stable major histocompatibility complex (MHC)-peptide complexes. In addition, vaccination with DC pulsed with the modified peptide elicited a robust, specific CTL response, significantly inhibited tumor growth and prolonged the lifespan of the mice.
CONCLUSIONS: The heparanase epitope modified by ER retrieval signal can be considered an ideal tumor vaccine, and may represent a new strategy for cancer immunotherapy in the clinic.