{"id":{"repo_id":"drake","oai_identifier":"oai:escholarshare.drake.edu:2092/462"},"canonical_url":"https://search.dev.ndltd.org/etd/drake/oai:escholarshare.drake.edu:2092/462","repository":{"repo_id":"drake","name":"Drake University","base_url":"https://escholarshare.drake.edu/server/oai/request"},"display":{"title":"Gene Therapy for Osteosarcoma : \"In Vitro\" Characterization of Five Tumor Cell Lines and Development of Treatment Models \"In Vivo\"","abstract":"Four human osteosarcoma cell lines (MNNG, TE85, MG63, and G292) and a human-derived osteosarcoma metastatic to murine lung (MLM) were transduced \"in vitro\" using retroviral vectors containing the Herpes simplex thymidine kinase (HS-tk), human interleukin 2 (IL2). and B-galactosidase (BAG) genes. Each osteosarcoma cell line was stably transduced, and the HS-tk gene effectively conferred ganciclovir (GCV) susceptibility to transduced cells. Each cell line showed a bystander effect (whereby wild type tumor cells are killed by co-incubation with HS-tk positive tumor cells and GCV). MNNG cells were used to develop a series of experiments in athymic nude mice to investigate the utility of gene therapy for the treatment of experimental osteosarcomas. Subcutaneous implants of mixtures of tumor cells and HS-tk vector producer cells (vpc) resulted in the development of tumors which were completely cured upon administration of GCV. Subcutaneous implant of mixtures of transduced and wild-type cells resulted in a potent bystander effect upon administration of GCV, with complete tumor ablation when as little as ten percent of the cells were HS-tk positive. A significant anti-tumor response was seen against primary tumors comprised of unmodified cells when a secondary tumor of transduced cells was induced at a distance of one centimeter, which supports a soluble bystander factor model. The presence of IL2-transduced cells significantly improved the efficacy of treatment, suggesting a synergy between the HS-tk and IL2 gene products. A significant anti-tumor response was seen in the treatment of established osteosarcomas by the injection of HS-tk vpc.","abstract_html":"Four human osteosarcoma cell lines (MNNG, TE85, MG63, and G292) and a human-derived osteosarcoma metastatic to murine lung (MLM) were transduced "in vitro" using retroviral vectors containing the Herpes simplex thymidine kinase (HS-tk), human interleukin 2 (IL2). and B-galactosidase (BAG) genes. Each osteosarcoma cell line was stably transduced, and the HS-tk gene effectively conferred ganciclovir (GCV) susceptibility to transduced cells. Each cell line showed a bystander effect (whereby wild type tumor cells are killed by co-incubation with HS-tk positive tumor cells and GCV). MNNG cells were used to develop a series of experiments in athymic nude mice to investigate the utility of gene therapy for the treatment of experimental osteosarcomas. Subcutaneous implants of mixtures of tumor cells and HS-tk vector producer cells (vpc) resulted in the development of tumors which were completely cured upon administration of GCV. Subcutaneous implant of mixtures of transduced and wild-type cells resulted in a potent bystander effect upon administration of GCV, with complete tumor ablation when as little as ten percent of the cells were HS-tk positive. A significant anti-tumor response was seen against primary tumors comprised of unmodified cells when a secondary tumor of transduced cells was induced at a distance of one centimeter, which supports a soluble bystander factor model. The presence of IL2-transduced cells significantly improved the efficacy of treatment, suggesting a synergy between the HS-tk and IL2 gene products. A significant anti-tumor response was seen in the treatment of established osteosarcomas by the injection of HS-tk vpc.","abstract_has_math":false,"creators":["Walling, Hobart W."],"institution":"Drake University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1995,"date_issued":"1995-02","date_published":"1995-02","updated_at":"2026-07-27T19:20:19Z","subjects":["Osteosarcoma","Cell lines","Gene therapy"],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["1995 .W158"],"render_values":[{"text":"1995 .W158","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2092/462","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Walling, Hobart W."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2006-11-27T16:55:28Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2006-11-27T16:55:28Z"]},{"key":"dc:date.issued","label":"Date","values":["1995-02"]},{"key":"dc:publisher","label":"Institution","values":["Drake University"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Osteosarcoma","Cell lines","Gene therapy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["1995 .W158"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2092/462"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["135 leaves. Advisor: Dean A. Hoganson"]},{"key":"dc:description.abstract","label":"Abstract","values":["Four human osteosarcoma cell lines (MNNG, TE85, MG63, and G292) and a human-derived osteosarcoma metastatic to murine lung (MLM) were transduced \"in vitro\" using retroviral vectors containing the Herpes simplex thymidine kinase (HS-tk), human interleukin 2 (IL2). and B-galactosidase (BAG) genes. Each osteosarcoma cell line was stably transduced, and the HS-tk gene effectively conferred ganciclovir (GCV) susceptibility to transduced cells. Each cell line showed a bystander effect (whereby wild type tumor cells are killed by co-incubation with HS-tk positive tumor cells and GCV). MNNG cells were used to develop a series of experiments in athymic nude mice to investigate the utility of gene therapy for the treatment of experimental osteosarcomas. Subcutaneous implants of mixtures of tumor cells and HS-tk vector producer cells (vpc) resulted in the development of tumors which were completely cured upon administration of GCV. Subcutaneous implant of mixtures of transduced and wild-type cells resulted in a potent bystander effect upon administration of GCV, with complete tumor ablation when as little as ten percent of the cells were HS-tk positive. A significant anti-tumor response was seen against primary tumors comprised of unmodified cells when a secondary tumor of transduced cells was induced at a distance of one centimeter, which supports a soluble bystander factor model. The presence of IL2-transduced cells significantly improved the efficacy of treatment, suggesting a synergy between the HS-tk and IL2 gene products. A significant anti-tumor response was seen in the treatment of established osteosarcomas by the injection of HS-tk vpc."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Gene Therapy for Osteosarcoma : \"In Vitro\" Characterization of Five Tumor Cell Lines and Development of Treatment Models \"In Vivo\""]}]}],"canonical_facts":{"dc:creator":["Walling, Hobart W."],"dc:date.accessioned":["2006-11-27T16:55:28Z"],"dc:date.available":["2006-11-27T16:55:28Z"],"dc:date.issued":["1995-02"],"dc:description":["135 leaves. Advisor: Dean A. Hoganson"],"dc:description.abstract":["Four human osteosarcoma cell lines (MNNG, TE85, MG63, and G292) and a human-derived osteosarcoma metastatic to murine lung (MLM) were transduced \"in vitro\" using retroviral vectors containing the Herpes simplex thymidine kinase (HS-tk), human interleukin 2 (IL2). and B-galactosidase (BAG) genes. Each osteosarcoma cell line was stably transduced, and the HS-tk gene effectively conferred ganciclovir (GCV) susceptibility to transduced cells. Each cell line showed a bystander effect (whereby wild type tumor cells are killed by co-incubation with HS-tk positive tumor cells and GCV). MNNG cells were used to develop a series of experiments in athymic nude mice to investigate the utility of gene therapy for the treatment of experimental osteosarcomas. Subcutaneous implants of mixtures of tumor cells and HS-tk vector producer cells (vpc) resulted in the development of tumors which were completely cured upon administration of GCV. Subcutaneous implant of mixtures of transduced and wild-type cells resulted in a potent bystander effect upon administration of GCV, with complete tumor ablation when as little as ten percent of the cells were HS-tk positive. A significant anti-tumor response was seen against primary tumors comprised of unmodified cells when a secondary tumor of transduced cells was induced at a distance of one centimeter, which supports a soluble bystander factor model. The presence of IL2-transduced cells significantly improved the efficacy of treatment, suggesting a synergy between the HS-tk and IL2 gene products. A significant anti-tumor response was seen in the treatment of established osteosarcomas by the injection of HS-tk vpc."],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["1995 .W158"],"dc:identifier.uri":["http://hdl.handle.net/2092/462"],"dc:language.iso":["en_US"],"dc:publisher":["Drake University"],"dc:subject":["Osteosarcoma","Cell lines","Gene therapy"],"dc:title":["Gene Therapy for Osteosarcoma : \"In Vitro\" Characterization of Five Tumor Cell Lines and Development of Treatment Models \"In Vivo\""],"dc:type":["Thesis"]},"updated_at":"2026-07-27T19:20:19Z"}