XAGE-1, A Gene Expressed in Multiple Cancers and Uses Thereof
Description of Invention:
The XAGE-1 gene is a human X-linked gene that is strongly expressed in breast cancer, lung cancer and several other cancers as well as normal testes. The largest open reading frame of the XAGE-1 transcript encodes a putative protein of 16.3 kD (p16) with a potential transmembrane domain at the amino terminus. In addition, the XAGE-1 transcript contains a second ATG in the reading frame corresponding to residue 66, which would encode a 9 kD protein (p9). In vitro transfection experiments using 293 T cells have revealed a 9 kD protein. However, the size of the endogenously expressed protein is not yet known. XAGE-1 shares homology with GAGE/PAGE proteins in the C-terminal end.
The invention relates to the fact that the XAGE-1 gene is expressed in a number of human cancers, specifically: breast, lung, prostate, pancreatic, and ovarian cancers. The proteins p9 and p16, immunogenic fragments thereof, analogs of these proteins, and nucleic acids encoding these proteins, fragments, or analogs, can be administered to persons with XAGE-1 expressing cancers to raise or augment an immune response to the cancer. The invention further provides nucleic acid sequences encoding the protein, as well as expression vectors, host cells, and antibodies to the proteins. Further, the invention provides immunoconjugates that comprise an antibody to p16 or to p9, and an effector molecule, such as a label, a radioisotope, or a toxin. The invention also provides methods of inhibiting the growth of XAGE-1 expressing cells by contacting them with immunoconjugates of an anti-p9 or p16 antibody and a toxic moiety. The invention also provides kits for the detection of p9 or p16 proteins in a sample. The XAGE-1 gene and encoded protein could be of value in the development of a cancer diagnostic and/or a cancer immunotherapy.
Inventors:
Ira H. Pastan (NCI) Xiu F. Liu (NCI) Byungkook Lee (NCI) Lee J. Helman (NCI)
Patent Status:
DHHS Reference No. E-161-2000/0 --
U.S. Provisional Application No. 60/229,684 filed 01 Sep 2000
PCT Application No. PCT/US01/27258 filed 31 Aug 2001, which published as WO 02/18584 on 07 Mar 2002
U.S. Patent Application No. 10/363,233 filed 18 Jul 2003
Licensing Status: Available for licensing on an exclusive or non-exclusive basis.
Portfolios: Cancer
Cancer -Diagnostics-In Vitro-DNA Based Cancer -Therapeutics-Immunoconjugates-Mab Cancer -Diagnostics Cancer -Therapeutics
For Additional Information Please Contact: David A. Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4632
Email: lambertsond@mail.nih.gov
Fax: (301) 402-0220
