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Adenovirus type 6 (Ad6), a species C human adenovirus, offers significant potential for cancer therapy due to its low seroprevalence compared to Adenovirus type 5 (Ad5) and its ability to evade Kupffer cells during systemic delivery. In this study, we developed a novel oncolytic adenovirus vector based on the Ad6 engineered to express human GM-CSF (Ad6-d24-GM) and evaluated its therapeutic efficacy in a novel immunocompetent, replication-permissive Syrian hamster model of CCA. Intratumoral administration of Ad6-d24-GM significantly suppressed tumor growth and prolonged survival without evidence of toxicity, as indicated by stable body weights and normal liver enzyme levels. Both Ad6-d24-GM and wild-type Ad6 induced robust infiltration of CD4+ and CD8+ T cells, as well as CD68+ macrophages within tumors, demonstrating activation of antitumor immunity. Notably, the Ad6-d24-GM group exhibited a statistically significant increase in CD68+ cells compared to wild-type Ad6, highlighting the immunomodulatory effect of GM-CSF transgene. These results demonstrate the oncolytic and immunostimulatory potential of Ad6-based vectors for CCA treatment and validate the Syrian hamster syngeneic CCA-OF model as a valuable platform for studying oncolytic adenovirus therapies.<\/jats:p>","DOI":"10.3390\/v17020162","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T05:24:31Z","timestamp":1737696271000},"page":"162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ad6-Based GM-CSF Expressing Vector Displays Oncolytic and Immunostimulatory Effects in an Immunocompetent Syrian Hamster Model of Cholangiocarcinoma"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7293-6815","authenticated-orcid":false,"given":"Daria S.","family":"Zabelina","sequence":"first","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3797-7731","authenticated-orcid":false,"given":"Ivan D.","family":"Osipov","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2806-5933","authenticated-orcid":false,"given":"Denis E.","family":"Maslov","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna V.","family":"Kovner","sequence":"additional","affiliation":[{"name":"Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Akad. Lavrentiev Ave., Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1142-184X","authenticated-orcid":false,"given":"Valeriia A.","family":"Vasikhovskaia","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0617-2473","authenticated-orcid":false,"given":"Diana S.","family":"Demina","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav E.","family":"Romanov","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6893-9782","authenticated-orcid":false,"given":"Ekaterina V.","family":"Shishkina","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Davydova","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7786-2464","authenticated-orcid":false,"given":"Sergey V.","family":"Netesov","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Novosibirsk State University, Pirogov 2, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita V.","family":"Romanenko","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/cco.2019.08.09","article-title":"Cholangiocarcinoma: A Site-Specific Update on the Current State of Surgical Management and Multi-Modality Therapy","volume":"9","author":"Turgeon","year":"2020","journal-title":"Chin. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Manthopoulou, E., Ramai, D., Dhar, J., Samanta, J., Ioannou, A., Lusina, E., Sacco, R., and Facciorusso, A. (2023). Cholangiocarcinoma in the Era of Immunotherapy. Vaccines, 11.","DOI":"10.3390\/vaccines11061062"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"TPS598","DOI":"10.1200\/JCO.2022.40.6_suppl.TPS598","article-title":"A Phase 3, Single-Arm Study of CG0070 in Subjects with Nonmuscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG)","volume":"40","author":"Uchio","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/s41591-023-02347-y","article-title":"Oncolytic DNX-2401 Virotherapy plus Pembrolizumab in Recurrent Glioblastoma: A Phase 1\/2 Trial","volume":"29","author":"Nassiri","year":"2023","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1200\/JCO.2023.41.16_suppl.4052","article-title":"Phase II Study of Telomelysin (OBP-301) in Combination with Pembrolizumab in Gastroesophageal (GEA) Adenocarcinoma","volume":"41","author":"Shah","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S1470-2045(24)00079-2","article-title":"LOAd703, an Oncolytic Virus-Based Immunostimulatory Gene Therapy, Combined with Chemotherapy for Unresectable or Metastatic Pancreatic Cancer (LOKON001): Results from Arm 1 of a Non-Randomised, Single-Centre, Phase 1\/2 Study","volume":"25","author":"Musher","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e010016","DOI":"10.1136\/jitc-2024-010016","article-title":"First-in-Human Clinical Outcomes with NG-350A, an Anti-CD40 Expressing Tumor-Selective Vector Designed to Remodel Immunosuppressive Tumor Microenvironments","volume":"12","author":"Naing","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_8","first-page":"1319","article-title":"Survivin Promoter-Based Conditionally Replicative Adenoviruses Target Cholangiocarcinoma","volume":"29","author":"Zhu","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1016\/j.jss.2008.12.016","article-title":"Oncolytic Gene Therapy Combined with Double Suicide Genes for Human Bile Duct Cancer in Nude Mouse Models","volume":"157","author":"Kojima","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2207668","DOI":"10.1002\/smll.202207668","article-title":"Three-in-One Oncolytic Adenovirus System Initiates a Synergetic Photodynamic Immunotherapy in Immune-Suppressive Cholangiocarcinoma","volume":"19","author":"Wang","year":"2023","journal-title":"Small"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/14760584.2019.1588113","article-title":"A Review of 65 Years of Human Adenovirus Seroprevalence","volume":"18","author":"Mennechet","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.virol.2010.10.041","article-title":"Characterization of Species C Human Adenovirus Serotype 6 (Ad6)","volume":"412","author":"Weaver","year":"2011","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Romanenko, M., Osipov, I., Netesov, S.V., and Davydova, J. (2021). Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101641"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11705","DOI":"10.1128\/JVI.01320-08","article-title":"Clearance of Adenovirus by Kupffer Cells Is Mediated by Scavenger Receptors, Natural Antibodies, and Complement","volume":"82","author":"Xu","year":"2008","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1038\/mt.2011.71","article-title":"Generation of a Kupffer Cell-Evading Adenovirus for Systemic and Liver-Directed Gene Transfer","volume":"19","author":"Khare","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.21873\/anticanres.13815","article-title":"Oncolytic Effect of Adenoviruses Serotypes 5 and 6 Against U87 Glioblastoma Cancer Stem Cells","volume":"39","author":"Romanenko","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Osipov, I.D., Vasikhovskaia, V.A., Zabelina, D.S., Kutseikin, S.S., Grazhdantseva, A.A., Kochneva, G.V., Davydova, J., Netesov, S.V., and Romanenko, M.V. (2023). Development of Oncolytic Vectors Based on Human Adenovirus Type 6 for Cancer Treatment. Viruses, 15.","DOI":"10.3390\/v15010182"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15021","DOI":"10.1038\/mto.2015.21","article-title":"Evaluation of Polymer Shielding for Adenovirus Serotype 6 (Ad6) for Systemic Virotherapy against Human Prostate Cancers","volume":"3","author":"Nguyen","year":"2016","journal-title":"Mol. Ther.-Oncolytics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/OV.S155946","article-title":"Oncolytic Adenovirus Ad657 for Systemic Virotherapy against Prostate Cancer","volume":"7","author":"Nguyen","year":"2018","journal-title":"Oncolytic Virother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1158\/1535-7163.MCT-12-0157","article-title":"MicroRNA Regulation of Oncolytic Adenovirus 6 for Selective Treatment of Castration-Resistant Prostate Cancer","volume":"11","author":"Zhang","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/CHC.S28079","article-title":"The Retinoblastoma Protein: A Master Tumor Suppressor Acts as a Link between Cell Cycle and Cell Adhesion","volume":"7","author":"Cress","year":"2014","journal-title":"Cell Health Cytoskelet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1158\/0008-5472.CAN-12-0806","article-title":"Immune-Dependent and Independent Antitumor Activity of GM-CSF Aberrantly Expressed by Mouse and Human Colorectal Tumors","volume":"73","author":"Urdinguio","year":"2013","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1007\/s11912-024-01611-9","article-title":"Talimogene Laherparepvec (T-VEC) and Emerging Intralesional Immunotherapies for Metastatic Melanoma: A Review","volume":"26","author":"Kalsi","year":"2024","journal-title":"Curr. Oncol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1158\/2326-6066.CIR-14-0058","article-title":"A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF\u2013Secreting Breast Tumor Vaccine for HER2+ Metastatic Breast Cancer","volume":"2","author":"Chen","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Koodie, L., Robertson, M.G., Chandrashekar, M., Ruth, G., Dunning, M., Bianco, R.W., and Davydova, J. (2019). Rodents Versus Pig Model for Assessing the Performance of Serotype Chimeric Ad5\/3 Oncolytic Adenoviruses. Cancers, 11.","DOI":"10.3390\/cancers11020198"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/B978-0-12-398342-8.00003-3","article-title":"Syrian Hamster as an Animal Model to Study Oncolytic Adenoviruses and to Evaluate the Efficacy of Antiviral Compounds","volume":"115","author":"Wold","year":"2012","journal-title":"Adv. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1128\/jvi.67.1.101-111.1993","article-title":"Pathogenesis of Adenovirus Type 5 Pneumonia in Cotton Rats (Sigmodon Hispidus)","volume":"67","author":"Prince","year":"1993","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1158\/0008-5472.CAN-05-3497","article-title":"Syrian Hamster as a Permissive Immunocompetent Animal Model for the Study of Oncolytic Adenovirus Vectors","volume":"66","author":"Thomas","year":"2006","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jia, Y., Wang, Y., Dunmall, L.S.C., Lemoine, N.R., Wang, P., and Wang, Y. (2023). Syrian Hamster as an Ideal Animal Model for Evaluation of Cancer Immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1126969"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1093\/neuonc\/noab128","article-title":"An Immune-Competent, Replication-Permissive Syrian Hamster Glioma Model for Evaluating Delta-24-RGD Oncolytic Adenovirus","volume":"23","author":"Phillips","year":"2021","journal-title":"Neuro. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.omto.2020.03.003","article-title":"Comparison of Clinically Relevant Oncolytic Virus Platforms for Enhancing T Cell Therapy of Solid Tumors","volume":"17","author":"Quixabeira","year":"2020","journal-title":"Mol. Ther.-Oncolytics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/jgm.700","article-title":"Enhanced Efficacy of Conditionally Replicating Herpes Simplex Virus (G207) Combined with 5-fluorouracil and Surgical Resection in Peritoneal Cancer Dissemination Models","volume":"7","author":"Nakano","year":"2005","journal-title":"J. Gene Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119494","DOI":"10.1016\/j.lfs.2021.119494","article-title":"A Tumorigenic Cell Line Derived from a Hamster Cholangiocarcinoma Associated with Opisthorchis Felineus Liver Fluke Infection","volume":"277","author":"Mordvinov","year":"2021","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kovner, A., Zaparina, O., Kapushchak, Y., Minkova, G., Mordvinov, V., and Pakharukova, M. (2022). Jagged-1\/Notch Pathway and Key Transient Markers Involved in Biliary Fibrosis during Opisthorchis Felineus Infection. Trop. Med. Infect. Dis., 7.","DOI":"10.3390\/tropicalmed7110364"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104274","DOI":"10.1016\/j.yexmp.2019.104274","article-title":"Characteristics of Liver Fibrosis Associated with Chronic Opisthorchis Felineus Infection in Syrian Hamsters and Humans","volume":"110","author":"Kovner","year":"2019","journal-title":"Exp. Mol. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"106282","DOI":"10.1016\/j.actatropica.2021.106282","article-title":"Time-Dependent Renal Pathologies Associated with the Liver Fluke Infection, Opisthorchiasis Felinea","volume":"228","author":"Kapushchak","year":"2022","journal-title":"Acta Trop."},{"key":"ref_37","unstructured":"R Core Team (2023). R Core Team R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using Lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.18637\/jss.v082.i13","article-title":"LmerTest Package: Tests in Linear Mixed Effects Models","volume":"82","author":"Kuznetsova","year":"2017","journal-title":"J. Stat. Softw."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Washington, I.M., and Van Hoosier, G. (2012). Clinical Biochemistry and Hematology. The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents, Elsevier.","DOI":"10.1016\/B978-0-12-380920-9.00003-1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.bbadis.2017.06.005","article-title":"Chemoresistance and Chemosensitization in Cholangiocarcinoma","volume":"1864","author":"Marin","year":"2018","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.jhep.2020.11.037","article-title":"CD40-Mediated Immune Cell Activation Enhances Response to Anti-PD-1 in Murine Intrahepatic Cholangiocarcinoma","volume":"74","author":"Diggs","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.jhep.2019.05.026","article-title":"Reduction of Immunosuppressive Tumor Microenvironment in Cholangiocarcinoma by Ex Vivo Targeting Immune Checkpoint Molecules","volume":"71","author":"Zhou","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Supimon, K., Sangsuwannukul, T., Sujjitjoon, J., Phanthaphol, N., Chieochansin, T., Poungvarin, N., Wongkham, S., Junking, M., and Yenchitsomanus, P. (2021). Anti-Mucin 1 Chimeric Antigen Receptor T Cells for Adoptive T Cell Therapy of Cholangiocarcinoma. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85747-9"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.critrevonc.2016.11.016","article-title":"Tumor Infiltrating Lymphocytes in Gastrointestinal Tumors: Controversies and Future Clinical Implications","volume":"110","author":"Solinas","year":"2017","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S1091-255X(02)00437-7","article-title":"Development of a Therapeutic Adenoviral Vector for Cholangiocarcinoma Combining Tumor-Restricted Gene Expression and Infectivity Enhancement","volume":"7","author":"Nagi","year":"2003","journal-title":"J. Gastrointest. Surg."},{"key":"ref_47","first-page":"1847","article-title":"Adenovirus Expressing P27KIP1 Induces Apoptosis against Cholangiocarcinoma Cells by Triggering Fas Ligand on the Cell Surface","volume":"50","author":"Yamamoto","year":"2003","journal-title":"Hepatogastroenterology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/cgt.2011.47","article-title":"Mining the Adenovirus Virome for Oncolytics against Multiple Solid Tumor Types","volume":"18","author":"Chen","year":"2011","journal-title":"Cancer Gene Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.virol.2009.08.038","article-title":"Characterization of Human Adenovirus Serotypes 5, 6, 11, and 35 as Anticancer Agents","volume":"394","author":"Shashkova","year":"2009","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1128\/JVI.80.4.1688-1699.2006","article-title":"A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques","volume":"80","author":"Capone","year":"2006","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/sj.onc.1203251","article-title":"A Mutant Oncolytic Adenovirus Targeting the Rb Pathway Produces Anti-Glioma Effect In Vivo","volume":"19","author":"Fueyo","year":"2000","journal-title":"Oncogene"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1053\/hupa.2002.127444","article-title":"Expression of G1-S Modulators (P53, P16, P27, Cyclin D1, Rb) and Smad4\/Dpc4 in Intrahepatic Cholangiocarcinoma","volume":"33","author":"Kang","year":"2002","journal-title":"Hum. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s00436-009-1548-0","article-title":"Alterations of Gene Expression of RB Pathway in Opisthorchis Viverrini Infection-Induced Cholangiocarcinoma","volume":"105","author":"Boonmars","year":"2009","journal-title":"Parasitol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1158\/1078-0432.CCR-21-3324","article-title":"Convection Enhanced Delivery of the Oncolytic Adenovirus Delta24-RGD in Patients with Recurrent GBM: A Phase I Clinical Trial Including Correlative Studies","volume":"28","author":"Kleijn","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.ygyno.2013.06.003","article-title":"A Phase I Clinical Trial of Ad5\/3-\u039424, a Novel Serotype-Chimeric, Infectivity-Enhanced, Conditionally-Replicative Adenovirus (CRAd), in Patients with Recurrent Ovarian Cancer","volume":"130","author":"Kim","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.etp.2005.09.006","article-title":"Effect of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) on 5-FU-Induced Ulcerative Mucositis in Hamster Buccal Pouches","volume":"57","author":"Cho","year":"2006","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kumar, A., Taghi Khani, A., Sanchez Ortiz, A., and Swaminathan, S. (2022). GM-CSF: A Double-Edged Sword in Cancer Immunotherapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.901277"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40425-016-0121-5","article-title":"Phase I Study with ONCOS-102 for the Treatment of Solid Tumors\u2014An Evaluation of Clinical Response and Exploratory Analyses of Immune Markers","volume":"4","author":"Ranki","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1093\/neuonc\/noy082","article-title":"Oncolytic Virotherapy in Glioblastoma Patients Induces a Tumor Macrophage Phenotypic Shift Leading to an Altered Glioblastoma Microenvironment","volume":"20","author":"Kleijn","year":"2018","journal-title":"Neuro. Oncol."},{"key":"ref_60","first-page":"440","article-title":"An Open Label, Single-Arm, Phase II Multicenter Study of the Safety and Efficacy of CG0070 Oncolytic Vector Regimen in Patients with BCG-Unresponsive Non\u2013Muscle-Invasive Bladder Cancer: Interim Results","volume":"36","author":"Packiam","year":"2018","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40425-019-0510-7","article-title":"A Phase 1 Dose Escalation Study of the Oncolytic Adenovirus Enadenotucirev, Administered Intravenously to Patients with Epithelial Solid Tumors (EVOLVE)","volume":"7","author":"Machiels","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e003255","DOI":"10.1136\/jitc-2021-003255","article-title":"Phase I, Multicenter, Open-Label Study of Intravenous VCN-01 Oncolytic Adenovirus with or without Nab-Paclitaxel plus Gemcitabine in Patients with Advanced Solid Tumors","volume":"10","author":"Macarulla","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.surg.2015.01.006","article-title":"Oncolytic Adenovirus Expressing Interferon Alpha in a Syngeneic Syrian Hamster Model for the Treatment of Pancreatic Cancer","volume":"157","author":"LaRocca","year":"2015","journal-title":"Surgery"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s10024-002-0063-4","article-title":"Adenovirus Ascending Cholangiohepatitis","volume":"6","author":"Jaffe","year":"2003","journal-title":"Pediatr. Dev. 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