Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in preclinical studies and is currently being assessed in phase I clinical trials. It is well established that there is an immune component to the bystander effect observed with other systems such as thymidine kinase and cytosine deaminase; however, such an effect has not previously been described using NR. We have preliminary data suggesting an immune bystander effect with NR to further examine these effects and their potential enhancement by cytokines, an adenoviral vector containing CMV-NR, an internal ribosome entry site (IRES) and the gene for murine GM-CSF (mGM-CSF) was constructed. The NR-GM-CSF virus was validated in 2 experimental models and demonstrated increased therapeutic efficacy in the MC26 murine colorectal tumour model. These data illustrate that the combination of suicide gene therapy using NR and CB1954 with immune stimulation via GM-CSF gives an improved response compared to either modality alone and suggests that the immune component of this response may be beneficial in combating unresectable, metastatic disease and preventing tumour recurrence.

Original publication

DOI

10.1002/ijc.10916

Type

Journal article

Journal

Int J Cancer

Publication Date

10/03/2003

Volume

104

Pages

104 - 112

Keywords

Adenocarcinoma, Adenoviruses, Human, Adjuvants, Immunologic, Animals, Antineoplastic Agents, Alkylating, Aziridines, Bystander Effect, Colorectal Neoplasms, Combined Modality Therapy, Cytomegalovirus, Defective Viruses, Drug Resistance, Neoplasm, Escherichia coli Proteins, Female, Genes, Genes, Synthetic, Genetic Therapy, Genetic Vectors, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Immunotherapy, Mesothelioma, Mice, Mice, Inbred BALB C, Neoplasm Transplantation, Nitroreductases, Prodrugs, Specific Pathogen-Free Organisms, Tumor Cells, Cultured