PLGA microspheres
PLGA microspheres

PLGA microspheres

Poly(D,L-lactide-co-glycolide) (PLGA) microspheres are biodegradable antigen delivery devices for loading of dendritic cells with antigen and toll-like receptor ligand in vitro and in vivo. They possess useful characteristics such as an adjustable drug release profile and a very high encapsulation efficiency. Dendritic cells efficiently take up the microspheres, process the microencapsulated antigens and present them on MHC class I and II molecules. Vaccination of mice with these two compound microspheres led to robust CTL responses strong enough to eliminate pre-established model tumors and to protect mice from vaccinia virus infection. Moreover, we could show that immunotherapy with microspheres charged with lysates of prostate carcinoma cells together with the toll-like receptor ligands CpG oligonucleotides and polyI:C interferes with the growth of prostate carcinoma in  the preclinical transgenic adenocarcinoma mouse prostate (TRAMP) model, which closely resembles the human disease.

Selected readings

  • Herrmann, V.L., Wieland, D.E., Legler, D.F., Wittmann, V., Groettrup, M. (2016)The STEAP1262-270 Peptide Encapsulated into PLGA Microspheres Elicits Strong Cytotoxic T Cell Immunity in HLA-A*0201 Transgenic Mice – a New Approach to Immunotherapy against Prostate Carcinoma. Prostate. 76(5):456-68.
  • Herrmann VL, Hartmayer C, Planz O , Groettrup M. (2015) Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease. J Control Release Aug 12;216:121-131. doi: 10.1016/j.jconrel.2015.08.019
  • Mueller M, Reichardt W, Koerner J and Groettrup M. (2012). Coencapsulation of tumor lysate and CpG-ODN in PLGA-microspheres enables successful immunotherapy of prostate carcinoma in TRAMP mice. J Control Release, 162(1): 159-66.
  • Mueller M, Schlosser E, Gander B , Groettrup M. - (2010) 'Tumor eradication by immunotherapy with biodegradable PLGA microspheres - an alternative to incomplete Freund's adjuvant' Int. J. Cancer 129(2): 407-16.
  • Fischer S, Schlosser E, Mueller M, Csaba N, Merkle HP, Groettrup M, Gander B. (2009). - Concomitant delivery of a CTL-restricted peptide antigen and CpG ODN by PLGA microparticles to induce cellular response. - J Drug Target, 17(8): 652-61.
  • Schlosser E, Mueller M, Fischer S, Basta S, Busch DH, Gander B, Groettrup M. – 2008. – TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses. – Vaccine 26(13):1626-1637.
  • Fischer, S., Uetz-von Allmen, E., Waeckerle-Men, Y., Groettrup, M., Merkle, H. P., Gander, B. (2007). Dendritic cells preserve their phenotype and functionality upon phagocytosis of polyelectroclyte-coated PLGA microparticles. Biomaterials 28: 994-1004.
  • Waeckerle-Men, Y., Uetz-von Allmen, E., Gander, B., Scandella, E., Schlosser, E., Schmidtke, G., Merkle, H. P., and Groettrup, M. (2006). Encapsulation of proteins and peptides into biodegradable poly(D,L-lactide-co-glycolide) microspheres prolongs and enhances antigen presentation by human dendritic cells. Vaccine: 24, 1847-1857.
  • Waeckerle-Men, Y., Scandella, E., Uetz-von Allmen, E., Ludewig, B., Gillessen, S., Merkle, H. P., Gander, B., and Groettrup, M. (2004). Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable PLGA microspheres for DC-vaccination. J. Immunol. Methods: 287, 109-124