TARGETED FUSION PROTEINS FOR CANCER THERAPY

摘要

The invention relates to fusion proteins useful as therapeutics against cancer. The fusion protein comprises of cell-targeting moiety and apoptosis-inducing moiety. Cell-targeting moiety and apoptosis-inducing moiety are linked by a flexible linker, which are specifically recognized by cancer specific protease and cleaved in situ to release the apoptotic domain. In particular, the invention is illustrated by a recombinant fusion protein between human Vasoactive Intestinal Peptide (VIP) and BH3 domain of Bcl2 family protein, linked by a linker that has site for cancer specific proteases. The fusion protein specifically targets VIP receptor over-expressing cancer cells and induces cell-specific apoptosis after cleavage at the linker site by cancer specific proteases. Such fusion proteins are useful for the delivery of therapeutic/apoptotic moiety (peptides) to specific cells with perturbed expression of, but not limited to neuropeptide receptors.