title: Engineering better immunotherapies via RNA interference.
abstract: The therapeutic potential of dendritic cell (DC) cancer vaccines has gained momentum in recent years. However, clinical data indicate that antitumor immune responses generally fail to translate into measurable tumor regression. This has been ascribed to a variety of tolerance mechanisms, one of which is the expression of immunosuppressive factors by DCs and T cells. With respect to cancer immunotherapies, these factors antagonise the ability to induce robust and sustained immunity required for tumor cell eradication. Gene silencing of immunosuppressive factors in either DCs or adoptive transferred T cells enhanced anti-tumor immune responses and significantly inhibited tumor growth. Therefore, engineered next generation of DC vaccines or adoptive T-cell therapy should include immunomodulatory siRNAs to release the "brakes" imposed by the immune system. Moreover, the combination of gene silencing, antigen targeting to DCs and cytoplasmic cargo delivery will improve clinical benefits.
authors.affiliation: a Department of Immunology; Institute for Cancer Research ; Oslo University Hospital ; Montebello , Norway.
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D006801:Humans; D056747:Immunomodulation / Q000235:genetics* / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
chemical_list: D019496:Cancer Vaccines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D034741:RNA, Small Interfering
keywords: AML, acute myeloid leukemia; CMV, human cytomegalovirus; CTLA4, T-lymphocyte-associated antigen 4; DC, Dendritic cells; Gal, galectin hTERT, human telomerase reverse transcriptase; IDO, indoleamine 2,3-dioxygenase; IL, interleukin; INF, interferon; NK, natural killer; PD1, programmed cell death; RNA interference; RNAi, RNA interference; SOCS1, suppressor of cytokine signaling; STAT, Signal transducer and activator of transcription; T-cell therapy; TCR, T cell receptor; TLR, toll like receptor; Treg, Regulatory T; cancer vaccine; gene silencing; immunotherapy; siRNA, small interfering RNA; targeted therapies