Delivery of Tumor Antigens to Dendritic Cells Using Biodegradable Microspheres

  • Ying Waeckerle-Men
  • Bruno Gander
  • Marcus Groettrup
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 109)


Poly(D,L-lactide-co-glycolide) (PLGA) polymers have been used for the production of biodegradable medical sutures and for controlled drug release for decades. Useful characteristics such as in vivo biodegradability, an adjustable release profile, and the very high encapsulation capacity have stimulated immunologists to explore PLGA microspheres (MS) as antigen delivery systems for vaccination for more than 15 yr. In previous studies aiming at the development of“single-dose” vaccines, direct immunization with PLGA MS containing various antigens induced strong and sustained immune responses. We have observed that human immature monocyte-derived dendritic cells (MoDC) prepared for clinical application are able to internalize high numbers of MS without negative effects on their pivotal properties. Furthermore, PLGA-MS-incorporated antigens are effectively processed for presentation on major histo-compatibility complex (MHC) class I and MHC class II molecules by dendritic cells (DCs) in vitro and induced strong cytotoxic T-lymphocyte (CTL) responses in vivo. Taken together, PLGA MS is a promising delivery vehicle for the improvement of current DC-based tumor vaccine protocols.

Key Words

Antigen processing dendritic cells immunotherapy microspheres poly(lactide-co-glycolide) vaccine delivery 


  1. 1.
    Nestle, F. O., Alijagic, S., Gilliet, M., et al. (1998) Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells. Nat. Med. 4,328–332.PubMedCrossRefGoogle Scholar
  2. 2.
    Thurner, B., Haendle, I., Roder, C., et al. (1999) Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J. Exp. Med. 190, 1669–1678.PubMedCrossRefGoogle Scholar
  3. 3.
    Ludewig, B., McCoy, K., Pericin, M., et al. (2001) Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells. J. Immunol. 166, 3678–3687.PubMedGoogle Scholar
  4. 4.
    Thomasin, C., Corradin, G., Men, Y., Merkle, H. P., and Gander, B. (1996) Tetanus toxoid and synthetic malaria antigen containing poly(lactide)/poly(lactide-co-glycolide) micro-spheres, importance of polymer degradation and antigen release for immune response. J. Control. Release 41,131–145.CrossRefGoogle Scholar
  5. 5.
    Johansen, P., Men, Y., Merkle, H. P., and Gander, B. (2000) Revisiting PLA/PLGA microspheres: an analysis of their potential in parenteral vaccination. Eur. J. Pharm. Bio-pharm. 50,129–146.CrossRefGoogle Scholar
  6. 6.
    Men, Y., Audran, R., Thomasin, C., et al. (1999) MHC class I-and class II-restricted processing and presentation of microencapsulated antigens. Vaccine 17,1047–1056.PubMedCrossRefGoogle Scholar
  7. 7.
    Walter, E., Dreher, D., Kok, M., et al. (2001) Hydrophilic poly(DL-lactide-co-glycolide) microspheres for the delivery of DNA to human-derived macrophages and dendritic cells. J. Control. Release 76,149–168.PubMedCrossRefGoogle Scholar
  8. 8.
    Waeckerle-Men, Y., Scandella, E., Uetz-von Allmen, E., et al. (2004) Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable poly(lactide-co-glycolide) microspheres for immunotherapy. J. Immunol. Meth. 287(1-2), 109–124.CrossRefGoogle Scholar
  9. 9.
    Men, Y., Thomasin, C., Merkle, H., Gander, B., and Corradin, G. (1995) A single administration of tetanus toxoid in biodegradable microspheres elicits T cell and antibody responses similar or superior to those obtained with aluminum hydroxide. Vaccine 13, 683–689.PubMedCrossRefGoogle Scholar
  10. 10.
    Men, Y., Gander, B., Merkle, H. P., and Corradin, G. (1996) Induction of sustained and elevated immune responses to weakly immunogenic synthetic malarial peptides by encapsulation in biodegradable polymer microspheres. Vaccine 14, 1442–1450.PubMedCrossRefGoogle Scholar
  11. 11.
    Men, Y., Tamber, H., Audran, R., Gander, B., and Corradin, G. (1997) Induction of a cytotoxic T lymphocyte response by immunization with a malaria specific CTL peptide entrapped in biodegradable polymer microspheres. Vaccine 15, 1405–1412.PubMedCrossRefGoogle Scholar
  12. 12.
    Peter K., Men, Y., Pantaleo, G., Gander, B, and Corradin, G. (2001) Induction of a cytotoxic T-cell response to HIV-1 proteins with short synthetic peptides and human compatible adjuvants. Vaccine 19, 4121–4129.PubMedCrossRefGoogle Scholar
  13. 13.
    Kovacsovics-Bankowski, M., Clark, K., Benacerraf, B., and Rock, K. L. (1993) Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages.Proc. Natl. Acad. Sci. USA 90, 4942–4946.PubMedCrossRefGoogle Scholar
  14. 14.
    Shen, Z., Reznikoff, G., Dranoff, G., and Rock, K. L. (1997) Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J. Immunol. 158, 2723–2730.PubMedGoogle Scholar
  15. 15.
    Ikuta, Y., Katayama, N., Wang, L. J., et al. (2002) Presentation of a major histocompat-ibility complex class 1-binding peptide by monocyte-derived dendritic cells incorporating hydrophobized polysaccharide-truncated HER2 protein complex: implications for a polyvalent immuno-cell therapy. Blood 99, 3717–3724.PubMedCrossRefGoogle Scholar
  16. 16.
    Audran, R., Peter, K., Dannull, J., et al. (2003) Micro-encapsulation of peptides prolongs their presentation to cytotoxic T cells by antigen presenting cells in vitro. Vaccine 21, 1250–1255.PubMedCrossRefGoogle Scholar
  17. 17.
    Sah, H. 1997. A new strategy to determine the actual protein content of poly(lactide-co-glycolide) microspheres. J. Pharm. Sci. 86, 1315–1318.Google Scholar
  18. 18.
    Scandella, E., Men, Y., Gillessen, S., Förster, R., and Groettrup, M. (2002) Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 100, 1354–1361.PubMedCrossRefGoogle Scholar
  19. 19.
    Panyam, J., Zhou, W. Z., Prabha, S., Sahoo, S. K., and Labhasetwar, V. (2002) Rapidendo-lysosomal escape of poly(D,L-lactide-co-glycolide) nanoparticles: implications fordrug and gene delivery. FASEB J. 16, 1217–1226.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Ying Waeckerle-Men
    • 1
  • Bruno Gander
    • 2
  • Marcus Groettrup
    • 3
  1. 1.Research DepartmentCantonal Hospital St. GallenSt. GallenSwitzerland
  2. 2.Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) ZürichZürichSwitzerland
  3. 3.Research DepartmentCantonal Hospital St. GallenSt. GallenSwitzerland

Personalised recommendations