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In Vivo Delivery of Peptides and Toll-like Receptor Ligands by Mannose-functionalized Polymeric Nanoparticles Induces Prophylactic and Therapeutic Anti-tumor Immune Responses in a Melanoma Model

Silvaa et al. J Control Release. (2014) - PMID: 25483429

Product(s) used in this publication:  PepTrack™ Peptide Libraries

Abstract:

We hypothesized that the co-entrapment of melanoma-associated antigens and the Toll-like receptor (TLR) ligands Poly(I:C) and CpG, known to be Th1-immunopotentiators, in mannose-functionalized aliphatic polyester-based nanoparticles (NPs) could be targeted to mannose receptors on antigen-presenting cells and induce anti-tumor immune responses. High entrapment efficiencies of antigens and immunopotentiators in 150nm NPs were obtained. The co-entrapment of the model antigen ovalbumin and the TLR ligands was crucial to induce high IgG2c/IgG1 ratios and high levels of IFN-γ and IL-2. Mannose-functionalization of NPs potentiated the Th1 immune response. The nanoparticulate vaccines decreased the growth rate of murine B16F10 melanoma tumors in therapeutic and prophylatic settings. The combination of mannose-functionalized NPs containing MHC class I- or class II-restricted melanoma antigens and the TLR ligands induced the highest tumor growth delay. Overall, we demonstrate that the multifunctional properties of NPs in terms of targeting and antigen/adjuvant delivery have high cancer immunotherapeutic potential.

Copyright © 2014 Elsevier B.V. All rights reserved.

KEYWORDS:

Antigen presenting cells; Cancer vaccine; Mannose receptor targeting; Melanoma; Nanoparticles; PLGA; TLR

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