title: A Tumor Mitochondria Vaccine Protects against Experimental Renal Cell Carcinoma.
abstract: Mitochondria provide energy for cells via oxidative phosphorylation. Reactive oxygen species, a byproduct of this mitochondrial respiration, can damage mitochondrial DNA (mtDNA), and somatic mtDNA mutations have been found in all colorectal, ovarian, breast, urinary bladder, kidney, lung, and pancreatic tumors studied. The resulting altered mitochondrial proteins or tumor-associated mitochondrial Ags (TAMAs) are potentially immunogenic, suggesting that they may be targetable Ags for cancer immunotherapy. In this article, we show that the RENCA tumor cell line harbors TAMAs that can drive an antitumor immune response. We generated a cellular tumor vaccine by pulsing dendritic cells with enriched mitochondrial proteins from RENCA cells. Our dendritic cell-based RENCA mitochondrial lysate vaccine elicited a cytotoxic T cell response in vivo and conferred durable protection against challenge with RENCA cells when used in a prophylactic or therapeutic setting. By sequencing mtDNA from RENCA cells, we identified two mutated molecules: COX1 and ND5. Peptide vaccines generated from mitochondrial-encoded COX1 but not from ND5 had therapeutic properties similar to RENCA mitochondrial protein preparation. Thus, TAMAs can elicit effective antitumor immune responses, potentially providing a new immunotherapeutic strategy to treat cancer.
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; Department of Bioscience and Biotechnology, University of Camerino, Camerino 62032, Italy; and.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pierini
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Chongyun
authors.initials: C
authors.lastname: Fang
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Stavros
authors.initials: S
authors.lastname: Rafail
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: John G
authors.initials: JG
authors.lastname: Facciponte
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Jialing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia 06122, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Sanctis
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Mark A
authors.initials: MA
authors.lastname: Morgan
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Mireia
authors.initials: M
authors.lastname: Uribe-Herranz
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
authors.forename: Janos L
authors.initials: JL
authors.lastname: Tanyi
authors.affiliation: Ovarian Cancer Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; facciabe@upenn.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Facciabene
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000517:prevention & control*; D051545:Cyclooxygenase 1 / Q000276:immunology* / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000276:immunology / Q000517:prevention & control*; D008565:Membrane Proteins / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins / Q000276:immunology* / Q000494:pharmacology; D009245:NADH Dehydrogenase / Q000276:immunology* / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse; D009245:NADH Dehydrogenase; C541921:ND5 protein, mouse