Timothy R Burns

US Patent:

20020048566, Apr 25, 2002

Filed:

Sep 13, 2001

Appl. No.:

09/950836

Inventors:

Wafik El-Deiry - Bryn Mawr PA, US
Eric Bernhard - Philadelphia PA, US
Timothy Burns - Philadelphia PA, US
E. McDonald - Philadelphia PA, US

International Classification:

A61K048/00
A61K038/17
C12N015/86

US Classification:

424/093210, 435/320100, 514/012000

Abstract:

This invention relates to modulating cellular apoptosis in an animal by regulating the quantity of functional KILLER/DR5 receptor protein molecules in the target cell(s) of said animal, increasing the effectiveness of certain therapies such as chemotherapy and radiotherapy. Such modulation increases the difference in toxicity response between target cell(s) and non-target cell(s) in response to a therapy or treatment and comprises upregulation of wild-type proteins in cells targeted for increased apoptosis or upregulation of loss-of-function proteins in cells targeted for decreased apoptosis. The methods of this invention comprise administering a nucleic acid sequence encoding a wild-type KILLER/DR5 receptor protein or a nucleic acid sequence encoding a loss-of-function mutant KILLER/DR5 receptor protein to said animal. The pharmaceutical compositions of this invention comprise a loss-of-function KILLER/DR5 receptor protein. The isolated nucleic acid sequences of this invention comprise wild-type KILLER/DR5 receptor nucleic acid sequence(s) bearing one or more point mutations at selected amino acid(s). A target of this invention is spleen and gastrointestinal cancer cells.