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US 11,633,458 B2Granted
Compositions and methods for treating melanoma
AssigneeUniversity of Virginia Patent Foundation
InventorsCraig L. Slingluff, Jr., Ileana S. Mauldin
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AssigneeUniversity of Virginia Patent Foundation
InventorsCraig L. Slingluff, Jr., Ileana S. Mauldin
Estimating the term…
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.
A method of inducing CXCL10 in a cancer cell and treating a subject in need thereof for cancer, wherein said method induces CXCL10 in cancer cells from said cancer, wherein said cancer is selected from the group consisting of melanoma, ovarian cancer, breast cancer, and head and neck cancer, said method comprising administering to a subject in need thereof a pharmaceutical composition consisting of an effective amount of interferon-gamma (IFNγ) and an effective amount of at least one agonist of a Toll-Like Receptor (TLR), and optionally an inducer of IFNγ, wherein said TLR is selected from the group consisting of TLR1, 2, 4, and 6, and wherein said at least one agonist is selected from the group consisting of a TLR1/2, a TLR2/6, and a TLR4 agonist, wherein said administering induces CXCL10 in a cancer cell at a synergistic level compared to a level induced when administering just said IFNγ or a level induced when administering just said at least one agonist of TLR, thereby treating a cancer selected from the group consisting of melanoma, ovarian cancer, breast cancer, and head and neck cancer.
Dependencies are inferred from the claim text.