Mannan-mediated gene delivery for cancer immunotherapy.
Recent years have seen a resurgence in interest in the development of efficient non-viral delivery systems for DNA vaccines and gene therapy. We have previously used oxidized and reduced mannan as carriers for protein delivery to antigen-presenting cells by targeting the receptors that bind mannose, resulting in efficient induction of cellular responses. In the present study, oxidized mannan and reduced mannan were used as receptor-mediated gene transfer ligands for cancer immunotherapy. In vivo studies in C57BL/6 mice showed that injection of DNA encoding ovalbumin (OVA) complexed to oxidized or reduced mannan-poly-L-lysine induced CD8 and CD4 T-cell responses as well as antibody responses leading to protection of mice from OVA+ tumours. Both oxidized and reduced mannan delivery was superior to DNA alone or DNA-poly-L-lysine. These studies demonstrate the potential of oxidized and reduced mannan for efficient receptor-mediated gene delivery in vivo, particularly as DNA vaccines for cancer immunotherapy.
Tang
Choon K
CK
Immunology and Vaccine Laboratory, Burnet Institute at Austin, Heidelberg, VIC, Australia.
Lodding
Jodie
J
Minigo
Gabriela
G
Pouniotis
Dodie S
DS
Plebanski
Magdalena
M
Scholzen
Anja
A
McKenzie
Ian F C
IF
Pietersz
Geoffrey A
GA
Apostolopoulos
Vasso
V
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008351:Mannans / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010084:Oxidation-Reduction; D011107:Polylysine / Q000276:immunology / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA; D011107:Polylysine; D010047:Ovalbumin