HUMAN FIBROBLAST GROWTH FACTOR 2 (FGF2) - CYTOTOXIC DRUG CONJUGATES FOR TARGETED THERAPY OF FGFR-RELATED CANCERS

摘要

The subject invention provides strategy for destroying cancer cells using targeting molecules fused with highly cytotoxic agents. A natural ligand of FGF receptor, the fibroblast growth factor 2 (FGF2) or engineered variants thereof are used for bioconjugation with a potent cytotoxic compound such as monomethyl auristatin E (MMAE) or auristatin Y to establish a delivery technique for effective killing cancer cells overexpressing FGFR. The FGF2 molecule and its engineered variants act as a delivery molecules specifically directing cytotoxic drug to cancer cell by binding to FGF receptors and in consequence, being internalized into the cell. Obtained conjugates showed a prominent cytotoxic effect toward FGFR – related cancer cells.