title: A generic RNA pulsed DC based approach for developing therapeutic intervention against nasopharyngeal carcinoma.
abstract: The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs). The RNA extracted from well-characterized highly immunogenic NPC cells (C666-1) was transfected into MoDCs. The formulated and characterized cationic liposomes were used to achieving efficient RNA transfection of immature DCs. Further, DCs were forcibly matured with a cytokine cocktail to achieve greater expression of MHC and co-stimulatory molecules. Moreover, our results did not see any effect of RNA or lipids on MoDCs phenotype or cytokine expression. RNA loaded DCs derived from HLA-A2-positive donors were shown to activate effector memory cytotoxic T lymphocytes (CTLs) specific for TAAg ligand expressed by C666-1 cells. Our results show the comparison of cytotoxic response mounted against RNA-loaded DCs with those directly stimulated by C666-1 tumor cells. Our findings suggest that DCs expressing tumor cell RNA primed naïve T cells show T cells priming with lesser cytotoxicity and cytokine secretion when exposed with with C666-1 tumor cells. These results surface the potential of DCs to deliver RNA in NPCs, sufficient presentation of RNA to provoke perdurable immune responses against nasopharyngeal carcinoma. Our results implies that DC based vaccine approach may be useful to develop therapeutic interventional approach in the form of vaccine to address NPCs.
authors.affiliation: a Department of Periodontics , College of Dental Medicine, Georgia Regents University , Augusta , GA , USA.|b Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway , Ahmedabad , Gujarat , India.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Tyagi
authors.affiliation: b Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway , Ahmedabad , Gujarat , India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Parmar
authors.affiliation: b Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway , Ahmedabad , Gujarat , India.
authors.forename: Naisargee
authors.initials: N
authors.lastname: Patel
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002277:Carcinoma; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D012313:RNA / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D012313:RNA
keywords: CTL response; Cytokines; DCs; DOTAP; HLA; Inflammation; NPC-Nasopharyngeal carcinoma; RNA; cationic liposomes