Induction of anti-tumor immunity by dendritic cells pulsed with an endoplasmic reticulum retrieval signal modifies heparanase epitope in mice.
OBJECTIVE
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.
Zhou
Kun
K
Department of Emergency, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Zhu
Huaping
H
Huang
Liang
L
Guo
Yanhong
Y
Yan
Yiqun
Y
D000818:Animals; D017951:Antigen Presentation; D019496:Cancer Vaccines; D048708:Cell Growth Processes; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D019763:Heparin Lyase / Q000138:chemical synthesis / Q000235:genetics; D007114:Immunization; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D019763:Heparin Lyase