Abstract
Melittin is the predominant component of bee venom with cell membrane-disrupting capability. To release melittin on cell surfaces to destroy tumor cell membranes, we designed a recombinant targeting toxin with an uPA cleavable link. It contains A Disintegrin-like domain of ADAM 15 to selectively deliver fusion protein to the surface of the tumor cells expressing integrin αvβ3, a toxin domain consisting of four repeats of N-terminal 22 amino acids of melittin, and an uPA cleavable link in between. The fusion protein named as ADAM-Conj-Mel was successfully expressed in Escherichia coli and can be cleaved by uPA as well as conditioned medium of SW1990 tumor cells. In vitro, ADAM-Conj-Mel efficiently inhibits proliferation of human melanoma (C32) tumor cells. In vivo, it reduces B16 tumor volume by approximately 80%. Our data suggested that ADAM-Conj-Mel is a protein with potential in clinical development for cancer therapy.
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