Interferon Boosts Efficacy

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Science  31 Jan 2014:
Vol. 343, Issue 6170, pp. 462-463
DOI: 10.1126/science.343.6170.462-d

Therapeutic monoclonal antibodies, several of which have shown impressive outcomes in clinical trials, are an exciting avenue for treating cancer. Resistance to antibody treatment remains a major challenge, however, and so strategies to overcome such resistance are needed. Yang et al. report on one such strategy: Taking the knowledge that an increase in type I interferons (IFNs) correlates positively with clinical outcome in several cancers and that type I IFNs can enhance antitumor immunity in some models, the authors tethered IFN-β to a monoclonal antibody targeting the epithelial growth factor receptor (EGFR), which is approved for use in treating metastatic colorectal cancer and head and neck cancer. In a variety of tumor mouse models, including antibody-resistant tumor models, the antibody-IFN therapy was more effective than antibody therapy alone. Mechanistic studies showed that IFN increases antitumor immune responses by enhancing antigen presentation to T cells by dendritic cells present in the tumor microenvironment. Delivery of the antibody-IFN therapy with an additional therapeutic monoclonal antibody enhanced the durability of the treatment, further supporting the idea that effective cancer immunotherapy will require hitting multiple targets.

Cancer Cell 25, 37 (2014).

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