Mauldin, Ileana S.;University of Virginia Patent Foundation;Slingluff Jr., Craig L.
发明人:
申请号：
EP14860949.8
公开号：
EP3065829A4
申请日:
2014.11.07
申请国别(地区):
EP
年份:
2017
代理人:
摘要：
Toll-like receptor (TLR) agonists can induce chemokine production. We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that TLR2/6 agonists (MALP-2 or FSL-1) synergize with interferon-gamma (IFNγ) to induce production of CXCL10 from melanoma cells. Furthermore, melanoma cells and immune cells freshly isolated from surgical specimens also respond to TLR2/6 agonists +IFNγ by upregulating CXCL10 production, compared to treatment with either agent alone. It is also disclosed herein that these compounds are useful in inducing CLXL10 in other types of cancer. Collectively, these data identify a novel synergy of TLR2/6 agonists +IFNγ for inducing CXCL10 production directly from melanoma cells, raising the possibility that intratumoral administration of these agents may improve immune signatures in melanoma and have value in combination with other immune therapies, by supporting T-cell migration into melanoma metastases.
