Coating of mannan on LPD particles containing HPV E7 peptide significantly enhances immunity against HPV-positive tumor.
OBJECTIVE
Previously, our laboratory has reported that liposome-protamine-DNA (LPD) nanoparticle is an effective delivery system for tumor-associated antigens. Mannan, which potentially targets antigen-presenting cells, was coated on LPD to further enhance its antitumor activity.


METHODS
Cholesterol-conjugated mannan was coated on LPD. The abilities of mannan-coated LPD to target antigen-presenting cells, to activate dendritic cells, and to induce antitumor immunity were investigated and compared to those of LPD alone.


RESULTS
Both in vitro and in vivo uptake of LPD showed that mannan-coated LPD particles were preferably taken up by dendritic cells and macrophages. In addition, the expression of co-stimulatory molecules CD80/CD86 on DC2.4 cells after co-incubation with mannan-coated LPD was significantly higher than that after co-incubation with LPD. A model major histocompatibility complex class I-restricted peptide antigen from HPV 16 E7 protein was incorporated into LPD to immunize mice against the growth of TC-1 tumor cells expressing E7 protein. Coating with mannan significantly enhanced both preventive and therapeutic activities of LPD/E7. Finally, the release of IFN-gamma from isolated splenocytes was significantly enhanced when mice were immunized with mannan-coated LPD/E7 than with LPD/E7 alone.


CONCLUSIONS
Targeting of the LPD/E7 to local draining lymph nodes by mannan is partially responsible for the enhanced anti-tumor activity.
Cui
Zhengrong
Z
Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Han
Su-Ji
SJ
Huang
Leaf
L
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen; D002478:Cells, Cultured; D002784:Cholesterol / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism*; D008351:Mannans / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D036103:Nanotechnology; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D010316:Particle Size; D011479:Protamines / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D008081:Liposomes; D008351:Mannans; D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011479:Protamines; C059731:oncogene protein E7, Human papillomavirus type 16; D004247:DNA; D002784:Cholesterol