Journal
JOURNAL OF CONTROLLED RELEASE
Volume 273, Issue -, Pages 1-12Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2018.01.013
Keywords
Indoleamine 2, 3-dioxygenase (IDO); Small interfering RNA (siRNA); Nanoparticle; Tyrosinase-related protein 2 (Trp2); Saccharomyces cerevisiae; Melanoma tumor
Funding
- National Natural Science Foundation of China [81371208, 81402837, 31401158]
- National Science and Technology Major Projects of New Drugs [2014ZX09102045-005, 2014ZX09102041-007]
- State Key Laboratory of Biochemical Engineering [2015KF-02]
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Therapeutic vaccine is a promising approach in cancer therapy. But tumor-associated antigen peptides have weak immunogenicity and cancer patients are often characterized by immunosuppression and tolerance, leading to less efficiency of immunotherapy. We here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive charges with a diameter of approximately 5 mu m, resulting in selective phagocytosis by APC cells. YCP-delivered siRNA and Trp2 successfully escaped from phagosomes, efficiently inhibited IDO expression in DCs, promoted the immune reaction of T cell against Trp2, increased the secretion of proin-flammatory cytokines such as IFN-gamma, TNF-alpha, and IL-6, and decreased the generation of regulatory T cells. Moreover, YCPs significantly inhibited melanoma tumor growth by alleviating immune tolerance and promoting Trp2-specific CD8(+) T cell immune response. These results suggest that Saccharomyces cerevisiae as a combined immunotherapeutic platform to simultaneously delivery IDO-siRNA and Trp2 epitope peptide is a promising vaccine system for melanoma treatment.
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