title: The anti-fibrotic effect of GV1001 combined with gemcitabine on treatment of pancreatic ductal adenocarcinoma.
abstract: GV1001 is a telomerase-based cancer vaccine made of a 16-mer telomerase reverse transcriptase (TERT) peptide, and human TERT, the rate-limiting subunit of the telomerase complex, is an attractive target for cancer vaccination. The aim of this study was to evaluate the effect of telomerase peptide vaccination, GV1001 combined with gemcitabine in treatment of pancreatic ductal adenocardinoma (PDAC). Human PDAC cell lines were used in vitro experiment and also, PDAC xenograft mice model was established using PANC1, AsPC1 and CD133+ AsPC1 (PDAC stem cell). Treatment groups were divided as follows; control, gemcitabine, GV1001, gemcitabine and GV1001 combination. The inflammatory cytokines were measured from the blood, and xenograft tumor specimens were evaluated. GV1001 treatment alone did not affect the proliferation or the apoptosis of PDAC cells. Gemcitabine alone and gemcitabine with GV1001 groups had significantly reduced in tumor size and showed abundant apoptosis compared to other treatment groups. Surprisingly, xenograft PDAC tumor specimens of gemcitabine alone group had been replaced by severe fibrosis whereas gemcitabine with GV1001 group had significantly less fibrosis. Blood levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β increased in gemcitabine alone group, however, it was decreased in gemcitabine with GV1001 group. GV1001 combined with gemcitabine treatment showed significant loss of fibrosis in tumor tissue as well as tumor cell death. Therefore, further investigation of GV1001 effect combined with gemcitabine treatment may give us useful insights to overcome the hurdle in anti-cancer drug delivery over massive fibrosis around PDACs.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joo Kyung
authors.initials: JK
authors.lastname: Park
authors.affiliation: Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yejin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Korea.|Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jane
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Department of Ophthalmology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Tae Wan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwnag
authors.affiliation: Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Laboratory of Vitamin C and Anti-Oxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Korea.|Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005355:Fibrosis; D006801:Humans; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D019098:Telomerase / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D010446:Peptide Fragments; D003841:Deoxycytidine; C514987:GV1001 peptide; D019098:Telomerase; D000093542:Gemcitabine
keywords: GV 1001; gemcitabine; pancreatic ductal adenocarcinoma; xenograft tumor model