Journal
IMMUNOTHERAPY
Volume 8, Issue 2, Pages 179-198Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/imt.15.109
Keywords
cancer; gene therapy; IL-12; immunotherapy; nonviral vectors; viral vectors
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Funding
- Spanish Health Ministry [FIS PI14/01442]
- Spanish Science Ministry [SAF 202-39578]
- European Regional Development Fund (FEDER)
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IL-12 is an immunostimulatory cytokine with strong antitumor properties. Systemic administration of IL-12 in cancer patients led to severe toxic effects, prompting the development of gene therapy vectors able to express this cytokine locally in tumors. Both nonviral and viral vectors have demonstrated a high antitumor efficacy in preclinical tumor models. Some of these vectors, including DNA electroporation, adenovirus and ex vivo transduced dendritic cells, were tested in patients, showing low toxicity and moderate antitumor efficacy. IL-12 activity can be potentiated by molecules with immunostimulatory, antiangiogenic or cytotoxic activity. These combination therapies are of clinical interest because they could lower the threshold for IL-12 efficacy, increasing the therapeutic potential of gene therapy and preventing the toxicity mediated by this cytokine.
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