Zhengrong Cui1, Su-Ji Han, Leaf Huang. 1. Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Abstract
PURPOSE: 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. CONCLUSION: Targeting of the LPD/E7 to local draining lymph nodes by mannan is partially responsible for the enhanced anti-tumor activity.
PURPOSE: 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. CONCLUSION: Targeting of the LPD/E7 to local draining lymph nodes by mannan is partially responsible for the enhanced anti-tumor activity.
Authors: M Fukasawa; Y Shimizu; K Shikata; M Nakata; R Sakakibara; N Yamamoto; M Hatanaka; T Mizuochi Journal: FEBS Lett Date: 1998-12-28 Impact factor: 4.124
Authors: T Nakanishi; J Kunisawa; A Hayashi; Y Tsutsumi; K Kubo; S Nakagawa; H Fujiwara; T Hamaoka; T Mayumi Journal: Biochem Biophys Res Commun Date: 1997-11-26 Impact factor: 3.575
Authors: A F Ochsenbein; P Klenerman; U Karrer; B Ludewig; M Pericin; H Hengartner; R M Zinkernagel Journal: Proc Natl Acad Sci U S A Date: 1999-03-02 Impact factor: 11.205