Targeting of co-encapsulated antigens and TLR agonists to DC endosomes using microspheres

We have obtained data from our work on biodegradable poly (D, L-lactide-co-glycolide) (PLGS) micropsheres (MS) coencapsulating ligands for endosomally expressed TLRs plus exogeneous Antigen (Ag) to deliver its cargo to endosomes of murine Dendritic cells (DCs), thus initiating TLR mediated DC maturation as well as processing of MHC class I and class II restricted epitopes.

In these studies we used as Ag either Ovalbumin, or rec. Prion-protein. In the latter system, a CD4 T cell response could be initiated. We also found that the DNA sugar backbone determines TLR9 activation. We found that abasic PD 2’ deoxyribose homopolymers act as weak TLR9 agonist and that DNA bases short of CpG-motifs enhance this agonist activity. In contrast phospho-thioate (PS) modified abasic 2’ deoxyribose homopolymers act as TLR9 (and TLR7) agonists, but CpG-motifs convert the antagonistic function into agonist-activity.

Interestingly, T cell immunity induced was preventive and therapeutic in infectious and tumor models. Since PLGA-MS have a safety history in man, these preclinical vaccination data are promising for use in human.

• molecule type
• Rec. Prion-protein,
• deoxyribonucleic acids,
• Major histocompatibility complex class II,
• toll-like receptor 7,
• Ovalbumin,
• poly(D,L-lactide-co-glycolide),
• Major histocompatibility complex class I,
• Toll like receptor 9,
• CD4

• cell component type
• endosome,
• Microsphere

• organism type
• Mus musculus

• cell type
• T cell,
• dendritic cell

• experimental design type
• cellular modification design experiment

created over 16 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]