title: hTERT mRNA dendritic cell vaccination: complete response in a pancreatic cancer patient associated with response against several hTERT epitopes.
abstract: Immunotherapy targeting the hTERT subunit of telomerase has been shown to induce robust immune responses in cancer patients after vaccination with single hTERT peptides. Vaccination with dendritic cells (DCs) transfected with hTERT mRNA has the potential to induce strong immune responses to multiple hTERT epitopes and is therefore an attractive approach to more potent immunotherapy. Blood samples from such patients provide an opportunity for identification of new, in vivo processed T-cell epitopes that may be clinically relevant. A 62-year-old female patient underwent radical surgery for a pancreatic adenocarcinoma. After relapse, she obtained stable disease on gemcitabine treatment. Due to severe neutropenia, the chemotherapy was terminated. The patient has subsequently been treated with autologous DCs loaded with hTERT mRNA for 3 years. Immunomonitoring was performed at regular intervals following start of vaccination and clinical outcome measured by CT and PET/CT evaluation. The patient developed an immune response against several hTERT-derived Th and CTL epitopes. She presently shows no evidence of active disease based on PET/CT scans. No serious adverse events were experienced and the patient continues to receive regular booster injections. We here provide evidence for the induction of hTERT-specific immune responses following vaccination of a pancreas cancer patient with DCs loaded with hTERT mRNA. These responses are associated with complete remission. A thorough analysis of this patient immune response has provided a unique opportunity to identify novel epitopes, associated with clinical effects. These will be included in future hTERT vaccines.
authors.affiliation: Section for Immunology, Oslo University Hospital and University of Oslo, Radiumhospitalet, Montebello, 0310, Oslo, Norway.
authors.forename: Else M Inderberg
authors.initials: EM
authors.lastname: Suso
authors.forename: Svein
authors.initials: S
authors.lastname: Dueland
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Rasmussen
authors.forename: Turid
authors.initials: T
authors.lastname: Vetrhus
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kvalheim
authors.forename: Gustav
authors.initials: G
authors.lastname: Gaudernack
mesh_terms: D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000276:immunology*; D014162:Transfection
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase