Extracellular matrix binding chimeric proteins and methods of use thereof
View Patent ↗The present invention provides chimeric polypeptides comprising a first polypeptide that binds to a component of extracellular matrix and a second polypeptide that provides for a therapeutic effect. The present invention further provides compositions, including pharmaceutical compositions, comprising a subject chimeric polypeptide. A subject chimeric polypeptide is useful in a variety of treatment, diagnostic, and research applications, which are also provided.
1. A fusion polypeptide comprising a hyaluronan-binding polypeptide fused to a heterologous polypeptide, wherein said hyaluronan-binding polypeptide consists of the amino acid sequence of SEQ ID NO:2.
2. The fusion polypeptide of claim 1 , wherein the heterologous polypeptide is a growth factor, an enzyme that activates a prodrug, an angiogenesis inhibitor, a chemoattractant polypeptide or a matrix metalloproteinase inhibitor.
3. The fusion polypeptide of claim 2 , wherein the growth factor is a growth factor selected from nerve growth factor, vascular endothelial growth factor, acid fibroblast growth factor, basic fibroblast growth factor, ciliary neurotrophic factor, brain derived neurotrophic factor, neurotrophin-3, epidermal growth factor, transforming growth factor-α, transforming growth factor-β, neurotrophin-4, GM-CSF, G-CSF, stromal derived factor-1, a bone morphogenetic protein, cardiotrophin-1, choline acetyltransferase development factor, oncostatin M, glial cell-line-derived neurotrophic factor, insulin, insulin-like growth factor-1, insulin-like growth factor-2, interleukin-6, leukemia inhibitor factor, neurite promoting factor, platelet-derived growth factor, protease nexin-1, S-100, transforming growth factor-β, and vasoactive intestinal peptide.
4. The polypeptide of claim 1 , wherein the heterologous polypeptide is selected from IL-2, IFN-α, IL-8, IFN-γ, IL-12, and IFN-β.
5. The fusion polypeptide of claim 2 , wherein the enzyme that activates a prodrug is cytosine deaminase.
6. A composition comprising the fusion polypeptide of claim 1 and a buffer.
7. A composition comprising: a) the fusion polypeptide of claim 1 ; and b) a pharmaceutically acceptable excipient.
8. The composition of claim 7 , wherein the composition further comprises a cancer chemotherapeutic agent.