RESUMEN
The topic of cancer stem cells (CSCs) is of significant importance due to its implications in our understanding of the tumor biology as well as the development of novel cancer therapeutics. However, the question of whether targeting CSCs can hamper the growth of tumors remains mainly unanswered due to the lack of specific agents for this purpose. To address this issue, we have developed the first mutated version of herpes simplex virus-1 that is transcriptionally targeted against CD133+ cells. CD133 has been portrayed as one of the most important markers in CSCs involved in the biology of a number of human cancers, including liver, brain, colon, skin, and pancreas. The virus developed in this work, Signal-Smart 2, showed specificity against CD133+ cells in three different models (hepatocellular carcinoma, colorectal cancer, and melanoma) resulting in a loss of viability and invasiveness of cancer cells. Additionally, the virus showed robust inhibitory activity against in vivo tumor growth in both preventive and therapeutic mouse models as well as orthotopic model highly relevant to potential clinical application of this virus. Therefore, we conclude that targeting CD133+ CSCs has the potential to be pursued as a novel strategy against cancer. Stem Cells 2018;36:1154-1169.
Asunto(s)
Antígeno AC133/genética , Herpesvirus Humano 1/fisiología , Neoplasias/genética , Neoplasias/terapia , Virus Oncolíticos/fisiología , Transcripción Genética , Antígeno AC133/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones Desnudos , Invasividad Neoplásica , Neoplasias/patología , Especificidad de Órganos , Fenotipo , Plásmidos/genética , Regiones Promotoras Genéticas/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In the interval between the publication of the seventh and eighth editions of the Guide for the Care and Use of Laboratory Animals (Guide), much has changed with regard to the regulation and funding of highly pathogenic biologic agents and toxins (Select Agents). Funding of research involving highly pathogenic agents has increased dramatically during this time, thus increasing the demand for facilities capable of supporting this work. The eighth edition of the Guide briefly mentions Select Agents and provides a limited set of references. Here we provide some background information regarding the relevant laws and regulations, as well as an overview of the programmatic requirements pertaining to the use of Select Agents, with a focus on use in animals.