Abstract
Antitumor immunity can be enhanced by the coordinated release and delivery of antigens and immune-stimulating agents to antigen-presenting cells via biodegradable vaccine carriers. So far, encapsulation of TLR ligands and tumor-associated antigens augmented cytotoxic T cell (CTLs) responses. Here, we compared the efficacy of the invariant NKT (iNKT) cell agonist alpha-galactosylceramide (alpha-GalCer) and TLR ligands (R848 and poly I:C) as an adjuvant for the full length ovalbumin (OVA) in PLGA nanoparticles. We observed that OVA+alpha-GalCer nanoparticles (NP) are superior over OVA+TLR-L NP in generating and stimulating antigen-specific cytotoxic T lymphocytes without the need for CD4+ T cell help. Not only a 4-fold higher induction of antigen-specific T cells was observed, but also a more profound IFN-gamma secretion was obtained by the addition alpha-GalCer. Surprisingly, we observed that mixtures of OVA containing NP with alpha-GalCer were ineffective, demonstrating that co-encapsulation of both alpha-GalCer and antigen within the same nanoparticle is essential for the observed T cell responses. Moreover, a single immunization with OVA+alpha-GalCer NP provided substantial protection from tumor formation and even delayed the growth of already established tumors, which coincided with a prominent and enhanced antigen-specific CD8+ T cell infiltration. The provided evidence on the advantage of antigen and alpha-GalCer coencapsulation should be considered in the design of future nanoparticle vaccines for therapeutic purposes.
