An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed recombinant yeast vaccine inhibits melanoma tumor growth in mice

• Published in: Journal of controlled release 2018-03, Vol.273, p.1-12
• Main Authors: Liu, Dong-qun, Lu, Shuai, Zhang, Ling-xiao, Ji, Mei, Liu, Shu-ying, Wang, Shao-wei, Liu, Rui-tian
• Format: Article
• Language: English
• Subjects: Indoleamine 2, 3-dioxygenase (IDO); Melanoma tumor; Nanoparticle; Saccharomyces cerevisiae; Small interfering RNA (siRNA); Tyrosinase-related protein 2 (Trp2)
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2018.01.013

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 5μm, 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 proinflammatory cytokines such as IFN-γ,TNF-α, 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. [Display omitted]