title: Suicide gene therapy of rhabdomyosarcoma.
abstract: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and young adulthood. Conventional treatment consisting of surgery, chemotherapy and radiotherapy can be insufficient, as long-term survival chances decrease dramatically when cancer recurrence occurs. Due to this fact, efficient treatment of this cancer is still a demanding issue, thus, novel and innovative therapies have to be considered as a part of combined treatment. In the present study, we present effective suicide gene therapy of rhabdomyosarcoma cell line Rh30 involving herpes simplex thymidine kinase (HSV-TK) and ganciclovir (GCV). Transduction of rhabdomyosarcoma cells using lentiviral vectors allowed efficient introduction of HSV-TK gene. In this study we proved high susceptibility of modified cells to ganciclovir resulting in eradication of cancer cells both in vitro and in vivo. Our data revealed strong gap junctional intercellular communication in examined cell line responsible for elimination of unmodified cells by bystander effect, even if HSV-TK-expressing cells comprise only 20% of cultured cells. Moreover, investigated approach is also efficient in vivo, where complete remission of tumors upon only 14 days of systemic administration of GCV can be observed. Obtained results suggest that HSV-TK suicide gene therapy is very promising concept in future clinical studies concerning rhabdomyosarcoma.
authors.affiliation: Department of Transplantation, Faculty of Clinical Immunology and Transplantation, Jagiellonian University Medical College, 30-663 Krakow, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Konieczny
authors.affiliation: Department of Transplantation, Faculty of Clinical Immunology and Transplantation, Jagiellonian University Medical College, 30-663 Krakow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Sułkowski
authors.affiliation: Department of Transplantation, Faculty of Clinical Immunology and Transplantation, Jagiellonian University Medical College, 30-663 Krakow, Poland.
authors.forename: Bogna
authors.initials: B
authors.lastname: Badyra
authors.affiliation: Department of Transplantation, Faculty of Clinical Immunology and Transplantation, Jagiellonian University Medical College, 30-663 Krakow, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kijowski
authors.affiliation: Department of Transplantation, Faculty of Clinical Immunology and Transplantation, Jagiellonian University Medical College, 30-663 Krakow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Majka
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015774:Ganciclovir / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000628:therapy*; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D013937:Thymidine Kinase; D015774:Ganciclovir