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

Silva, Joana;Zupancic, Eva;Vandermeulen, Gaëlle;Oliveira, Vanessa G;Florindo, Helena F;et.al.
(2015) Journal of Controlled Release — Vol. 198, p. 91-103 (2015)

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Authors
  • Silva, Joana
    Author
  • Zupancic, Eva
    Author
  • Vandermeulen, GaëlleUCLouvain
    Author
  • Oliveira, Vanessa G
    Author
  • Préat, VéroniqueUCLouvain
    Author
  • Florindo, Helena F
    Author
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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.
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Silva, J., Zupancic, E., Vandermeulen, G., Oliveira, V. G., Salgado, A., Videira, M., Gaspar, M., Graca, L., Préat, V., & Florindo, H. F. (2015). 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. Journal of Controlled Release, 198, 91-103. https://doi.org/10.1016/j.jconrel.2014.11.033 (Original work published 2015)