ADENOVIRAL TARGETING, COMPOSITIONS AND METHODS THEREFOR

摘要

Polypeptides are disclosed comprising, in N-terminal-to-C-terminal order: an N-terminal segment of Ad5 fiber tail sequence; at least 2 pseudorepeats of an Ad5 fiber shaft domain sequence; a portion of a third Ad5 fiber shaft domain sequence; a carboxy-terminal segment of a T4 fibritin bacteriophage trimerization domain sequence; a linker sequence; and a camelid single chain antibody sequence. A camelid single chain antibody sequence can be against a human carcinoembryonic antigen. Also disclosed are nucleic acids encoding these polypeptides, and adenovirus vectors comprising the polypeptides. Methods are disclosed for treating a neoplastic disease. These methods can comprise administering an adenovirus vector comprising a disclosed polypeptide. Also disclosed are methods of targeting a vector to CEA-expressing cells. These methods comprise administering an adenovirus vector comprising a disclosed polypeptide. Methods can further comprise subjecting a subject to ionizing radiation in an amount effective for inducing CEA overexpression.