Tumor cells as cellular vehicles to deliver gene therapies to metastatic tumors.
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.
García-Castro
Javier
J
Unidad de Hematopoyesis y Terapia Génica, CIEMAT/Fundación Marcelino Botín, Madrid, Spain.
Martínez-Palacio
Jesús
J
Lillo
Rosa
R
García-Sánchez
Félix
F
Alemany
Ramón
R
Madero
Luis
L
Bueren
Juan A
JA
Ramírez
Manuel
M
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
D049452:Green Fluorescent Proteins