Skip to main content

Advertisement

SpringerLink
Log in

Coating of Mannan on LPD Particles Containing HPV E7 Peptide Significantly Enhances Immunity Against HPV-Positive Tumor

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

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-γ 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. N. Renkvist, C. Castelli, P. F. Robbins, and G. Parmiani. A listing of human tumor antigens recognized by T cells. Cancer Immunol. Immunother. 50:3-15 (2001).

    Google Scholar 

  2. G. Parmiani, M. Sensi, C. Castelli, L. Rivoltini, and A. Anichini. T-cell response to unique and shared antigens and vaccination of cancer patients. Cancer Immun. 2:6-15 (2002).

    Google Scholar 

  3. G. Ada Vaccines and vaccination. N. Engl. J. Med. 345:1042-1053 (2001).

    Google Scholar 

  4. L. Fong and E. G. Engleman. Dendritic cells in cancer immunotherapy. Annu. Rev. Immunol. 18:245-273 (2000).

    Google Scholar 

  5. S. Li and L. Huang. In vivo gene transfer via intravenous administration of cationic lipid-protamine-DNA (LPD) complexes. Gene Ther. 4:891-900 (1997).

    Google Scholar 

  6. S. Li, M. A. Rizzo, S. Bhattacharya, and L. Huang. Characterization of cationic lipid-protamine-DNA (LPD) complexes for intravenous gene delivery. Gene Ther. 5:930-937 (1998).

    Google Scholar 

  7. M. S. Whitmore, S. Li, and L. Huang. LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth. Gene Ther. 6:1867-1875 (1999).

    Google Scholar 

  8. M. Whitmore. Systemic administration of LPD prepared with CpG oligonucleotides inhibits the growth of established pulmonary metastases by stimulating innate and acquired antitumor immune responses. Cancer Immunol. Immunother. 50:503-14 (2001).

    Google Scholar 

  9. J. Dileo, R. Banerjee, M. Whitmore, J. V. Nayak, L. FaloJr., and L. Huang. Lipid-protamine-DNA-mediated antigen delivery to antigen-presenting cells results in enhanced anti-tumor immune responses. Mol. Ther. 7:640-648 (2003).

    Google Scholar 

  10. A. F. Ochsenbein, P. Klenerman, U. Karrer, B. Ludewig, M. Pericin, H. Hengartner, and R. Zinkernagel. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc. Natl. Acad. Sci. USA 96:2233-2238 (1999).

    Google Scholar 

  11. R. Zinkernagel, S. Ehl, P. Aichele, S. Oehen, T. Kundig, and H. Hengartner. Antigen localisation regulates immune responses in a dose-and time-dependent fashion: a geographical view of immune reactivity. Immunol. Rev. 156:199-209 (1997).

    Google Scholar 

  12. O. Akbari, N. Panjwani, S. Garcia, R. Tascon, D. Lowrie, and B. Stockinger. DNA vaccination: transfection and activation of dendritic cells as key events for immunity. J. Exp. Med. 189:169-178 (1999).

    Google Scholar 

  13. C. Condon. S. watkins, C. Celluzzi, K. Thompson, L. Falo, Jr. DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2:1122-1128 (1996).

    Google Scholar 

  14. A. Porgador, K. Irvine, A. Iwasaki, B. Barber, N. Restifo, and R. Germain. Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization. J. Exp. Med. 188:1075-1082 (1998).

    Google Scholar 

  15. U. Karrer, A. Althage, B. Odermatt, C. Roberts, S. Korsmeyer, S. Miyawaki, H. Hengartner, and R. M. Zinkernagel. On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice. J. Exp. Med. 185:2157-2170 (1997).

    Google Scholar 

  16. A. Avrameas, D. McIlroy, A. Hosmalin, B. Autran, P. Debre, M. Monsigy, A. C. Roche, P. Midoux. Expression of a mannose/fucose membrane lectin on human dendritic cells. Eur. J. Immunol. 26:394-400 (1996).

    Google Scholar 

  17. I. McKenzie, V. Apostolopoulos, C. Lees, P. Xing, S. Lofthouse, C. Osinski, V. Popouski, B. Acres, G. Pietersz. Oxidised mannan antigen conjugates preferentially stimulate T1 type immune responses. Vet. Immunol. Immunopathol. 63:185-190 (1998).

    Google Scholar 

  18. M. Fukasawa, Y. Shimizu, K. Shikata, M. Nakata, R. Sakakibara, N. Yamamoto, M. Hatanaka, T. Mizuochi. Liposome oligomannose-coated with neoglycolipid, a new candidate for a safe adjuvant for induction of CD8+ cytotoxic T lymphocytes. FEBS Lett. 441:353-356 (1998).

    Google Scholar 

  19. V. Apostolopoulos, N. Barnes, G. Pietersz, and I. McKenzie. Ex vivo targeting of the macrophage mannose receptor generates anti-tumor CTL responses. Vaccine 18:3174-3184 (2000).

    Google Scholar 

  20. M. Gadjeva, S. Thiel, and J. C. Jensenius. The mannan-binding-lectin pathway of the innate immune response. Curr. Opin. Immunol. 13:74-78 (2001).

    Google Scholar 

  21. N. Okada, T. Saito, K. Mori, Y. Masunag, Y. Fujii, J. Fujita, K. Fujimoto, T. Nakanishi, K. Tanaka, S. Nakagawa, T. Mayumi, T. Fujita, A. Yamamoto. Effects of lipofectin-antigen complexes on major histocompatibility complex class I-restricted antigen presentation pathway in murine dendritic cells and on dendritic cell maturation. Biochim. Biophys. Acta 1527:97-101 (2001).

    Google Scholar 

  22. S. Toda, N. Ishii, E. Okada, K. Kusakabe, H. Arai, K. Hamajima, I. Gorai, K. Nishioka, K. Okuda. HIV-1-specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomes and inhibited by anti-interferon-gamma antibody. Immunology 92:111-117 (1997).

    Google Scholar 

  23. Z. Cui and R. J. Mumper. Topical immunization using nanoengineered genetic vaccines. J. Control. Rel. 81:173-184 (2002).

    Google Scholar 

  24. J. C. Brown and R. C. Hunt. Lectins. Int. Rev. Cytol. 52:277-349 (1978).

    Google Scholar 

  25. M. Dittgen and B. Herbst. Zeta potential—fundamentals, measurement methods and application to pharmacy. Pharmazie 42:641-656 (1987).

    Google Scholar 

  26. L. East and C. M. Isacke. The mannose receptor family. Biochim. Biophys. Acta 1572:364-386 (2002).

    Google Scholar 

  27. C. Howard, J. Hope, S. Stephens, D. Gliddon, and G. Brooke. Co-stimulation and modulation of the ensuing immune response. Vet. Immunol. Immunopathol. 87:123-130 (2002).

    Google Scholar 

  28. S. M. Moghimi, A. E. Hawley, N. M. Christy, T. Gray, L. Illum, and S. S. Davis. Surface engineered nanospheres with enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes. FEBS Lett. 344:25-30 (1994).

    Google Scholar 

  29. T. Nakanishi, J. Kunisawa, A. Hayashi, Y. Tsutsumi, K. Kubo, S. Nakagawa, H. Fujiwara, T. Hamaoka, T. Mayumi. Positively charged liposome functions as an efficient immunoadjuvant in inducing immune responses to soluble proteins. Biochem. Biophys. Res. Commun. 240:793-797 (1997).

    Google Scholar 

  30. W. Jiang and D. S. Pisetsky. Enhancing immunogenicity by CpG DNA. Curr. Opin. Mol. Ther. 5:180-185 (2003).

    Google Scholar 

  31. B. Li, S. Li, T. Tan, D. B. Stolz, S. Watkins, L. Block, and L. Huang. Lyophilization of cationic lipid-protamine-DNA (LPD) complexes. J. Pharm. Sci. 89:355-364 (2000).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

    Zhengrong Cui, Su-Ji Han & Leaf Huang

Authors
  1. Zhengrong Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Su-Ji Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leaf Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leaf Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cui, Z., Han, SJ. & Huang, L. Coating of Mannan on LPD Particles Containing HPV E7 Peptide Significantly Enhances Immunity Against HPV-Positive Tumor. Pharm Res 21, 1018–1025 (2004). https://doi.org/10.1023/B:PHAM.0000029292.66792.4f

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:PHAM.0000029292.66792.4f

Search

Navigation