Research ArticleCancer

Genetic Engineering of Hematopoiesis for Targeted IFN-α Delivery Inhibits Breast Cancer Progression

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Science Translational Medicine  01 Jan 2014:
Vol. 6, Issue 217, pp. 217ra3
DOI: 10.1126/scitranslmed.3006353

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Toasting Tumor Immunotherapy

Tumor immunotherapy is a promising new strategy for cancer treatment but is somewhat limited by the immunosuppressive nature of the tumor microenvironment. Type I interferons (IFNs) have been shown to promote tumor immunity, but systemic toxicity has limited their use. Genetic engineering of hematopoietic stem cells (HSCs) is one way to modulate the immune response in the tumor microenvironment.

Now, Escobar et al. attempt to overcome this immunosuppression by introducing IFN-α into tumor-infiltrating macrophages. The authors developed a way to insert an IFN-α transgene into HSCs, but restrict IFN-α expression to differentiated monocytes. They then tested their cells in human hematochimeric mice. HSC engraftment and repopulation is inhibited if IFN-α is expressed in the less differentiated cells. However, here, the HSCs engraft and repopulate NSG mice. What’s more, these cells inhibit tumor progression and experimental metastasis in an autologous model of breast cancer, effectively reprogramming the tumor microenvironment.

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