Polyelectrolyte microcapsules: antigen delivery vehicles for potent induction of CTL responses (131.34)

Abstract

Developing effective cancer vaccines is thought to require the strong activation of cytotoxic T cells (CTLs) to kill transformed cells. Initiation of such CTL responses requires DCs presenting the antigen via the MHCI route, a feature hardly achievable using soluble antigens. Internalization of particulate antigens in contrast has been shown to strongly promote MHCI mediated antigen presentation. In this study, ovalbumin (OVA) was encapsulated in polyelectrolyte microcapsules (PEM), a new class of particles allowing efficient antigen encapsulation under non-denaturing conditions. OVA-loaded PEM strongly promoted MHCI mediated OVA presentation by DCs in vitro and in vivo. Being attractive tools to enhance antigen presentation, PEM however fail to activate DCs, a prerequisite for the initiation of potent CTL responses. To cope with this issue, we coated the surface of cationic PEM with oligonucleotides containing unmethylated CpG motifs, which are strong activators of DCs by triggering TLR9. Co-delivery of CpG and OVA-loaded microcapsules synergistically increased the strength of the CTL response, indicated by a dramatic increase in the number of IFN-γ secreting CTLs and a strongly enhanced killing of OVA peptide-pulsed splenocytes after adoptive transfer. Finally, immunisation with CpG-modified capsules was able to confer protective immunity against a lethal challenge with the highly aggressive OVA-transduced B16 melanoma, clearly demonstrating the potential of this approach.