Oxidized and reduced mannan mediated MUC1 DNA immunization induce effective anti-tumor responses.
DNA immunization is an attractive form of vaccination, which has shown promising results only in small animal models. There is a need to develop efficient gene delivery systems. We previously demonstrated that oxidized (OM) and reduced mannan (RM) complexed to ovalbumin DNA via poly-l-lysine (PLL), were able to generate potent immune responses in mice. Herein, we further investigated the suitability of OMPLL and RMPLL as carriers for mucin 1 (MUC1) DNA vaccination for cancer immunotherapy. Studies presented here showed that immune responses in C57BL/6 mice induced by OMPLL-MUC1 DNA and RMPLL-MUC1 DNA immunization were more immunogenic compared to MUC1 DNA alone. Moreover, tumor protection was evident at a dose as low as 0.5 microg. In addition, strong T cell responses were induced in HLA-A2 transgenic and human MUC1 transgenic mice. These results demonstrate the potential of OM and RM as efficient non-viral gene delivery carriers for DNA vaccines for use in cancer immunotherapy.
Immunology and Vaccine Laboratory, Burnet Institute (Austin Campus), Heidelberg, VIC, Australia.
Choon Kit
CK
Tang
Kuo-Ching
KC
Sheng
Dodie
D
Pouniotis
Sandra
S
Esparon
Hye-Youn
HY
Son
Chul-Woo
CW
Kim
Geoffrey A
GA
Pietersz
Vasso
V
Apostolopoulos
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D008351:Mannans / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control; D010084:Oxidation-Reduction; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000276:immunology* / Q000378:metabolism
D019496:Cancer Vaccines; D016207:Cytokines; D015789:HLA-A2 Antigen; C060192:MUC1 protein, human; D008351:Mannans; D018396:Mucin-1; D019444:Vaccines, DNA