Directed antigen presentation using polymeric microparticulate carriers degradable at lysosomal pH for controlled immune responses

Young Jik Kwon, Stephany M. Standley, Andrew P. Goodwin, Elizabeth R. Gillies, Jean Frechet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The types of the immune responses generated against an antigen are determined by the intracellular fate of the antigen. Endogenous antigens are processed in the cytoplasm and initiate cytotoxic T lymphocyte (CTL) activation. In contrast, exogenous antigens are degraded in the lysosome (or phagolysosome) of antigen presenting cells (APCs), and induce antibody-mediated immune responses and assist CTL activation. Therefore, maximizing a desired response by controlling delivery pathways is indispensable in vaccine development and immunotherapy. New cleavable microparticles have been prepared for use as protein-based vaccine carriers by polymerizing water soluble monomers including a newly developed aliphatic monomer with a pendant primary amine group and a cleavable acetal linkage with a wholly aliphatic cleavable acetal cross-linker. Incorporation of the cleavable amine monomer in the polymerization mixture increased the encapsulation efficiency of a model antigen, ovalbumin. Ex vivo assays showed that the composition of the particles greatly affected the magnitude and the pathway of antigen presentations, which determine the type of immune responses. The degradable particles synthesized with the new cross-linker enhanced MHC I antigen presentation 2-3-fold over nondegradable particles. It was also found that, by adding 10% cationic cleavable monomers to the microparticles, MHC I restricted antigen presentation was enhanced ca. 75 times over that achieved with nondegradable particles. The microparticles introduced in this study can be further used for targeting and gene delivery due to functionalizable and cleavable cationic monomers in addition to degradability.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalMolecular Pharmaceutics
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • Acetal cross-linker and monomer
  • Antigen presentation
  • CTL activation
  • Cancer vaccine
  • Controlled immune response
  • Microparticle

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

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