LAUSR

&NA; 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 &mgr;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 proinflammatory cytokines such as IFN‐&ggr;,TNF‐&agr;, 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.