Semaphorins are a versatile family of membrane bound and soluble proteins, which mainly regulate focal adhesion assembly/disassembly and induce cytoskeletal remodeling, thus affecting cell shape, cell attachment to extracellular matrix, cell mobility and cell migration. Semaphorins have been shown to participate in many processes, including immune response, angiogenesis and lymphangiogenesis. Class 3 semaphorins (Sema3), which bind to neuropilin receptors, are known to play a distinct role in promoting angiogenesis. Sema3 have also been implicated in tumor progression and is highly expressed in metastatic tumor cells.
The researchers have developed a method of selecting and using semaphorins for treating angiogenesis-related pathologies, such as cancer, that is based on: (a) profiling the Sema receptor expression in the specific tumor, and (b) specific targeting of that receptor using a relevant semaphorin or a variant thereof. They have further developed variants of Sema3C comprising modifications in furin-like protein convertase (FPPC) cleavage sites, which render the sites resistant to cleavage. Sema 3C and its variant have been shown to inhibit blood vessel formation and to induce collapse of lymphatic endothelial cells.
- Personalized therapy enabled by companion diagnostics
Applications and Opportunities
- Cancer therapy
- Treatment of angiogenesis-related disease
- Treatment of Age-related Macular Degeneration (AMD)