title: Tumor cells as cellular vehicles to deliver gene therapies to metastatic tumors.
abstract: A long-pursued goal in cancer treatment is to deliver a therapy specifically to metastases. As a result of the disseminated nature of the metastatic disease, carrying the therapeutic agent to the sites of tumor growth represents a major step for success. We hypothesized that tumor cells injected intravenously (i.v.) into an animal with metastases would respond to many of the factors driving the metastatic process, and would target metastases. Using a model of spontaneous metastases, we report here that i.v. injected tumor cells localized on metastatic lesions. Based on this fact, we used genetically transduced tumor cells for tumor targeting of anticancer agents such as a suicide gene or an oncolytic virus, with evident antitumoral effect and negligible systemic toxicity. Therefore, autologous tumor cells may be used as cellular vehicles for systemic delivery of anticancer therapies to metastatic tumors.
authors.affiliation: Unidad de Hematopoyesis y Terapia Génica, CIEMAT/Fundación Marcelino Botín, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Castro
authors.forename: Jesús
authors.initials: J
authors.lastname: Martínez-Palacio
authors.forename: Rosa
authors.initials: R
authors.lastname: Lillo
authors.forename: Félix
authors.initials: F
authors.lastname: García-Sánchez
authors.forename: Ramón
authors.initials: R
authors.lastname: Alemany
authors.forename: Luis
authors.initials: L
authors.lastname: Madero
authors.forename: Juan A
authors.initials: JA
authors.lastname: Bueren
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramírez
mesh_terms: D000818:Animals; D024201:Bystander Effect; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014780:Viruses / Q000235:genetics
chemical_list: D049452:Green Fluorescent Proteins