A new method for targeting solid tumors using gene therapy

Cancer is the second leading cause of death in United States and it is estimated that there will be approximately 600,000 deaths caused by cancer in 2006. Due to the high incidence of death from cancer despite the use of current therapies, there is a strong need for targeted therapeutic approaches such as gene therapy. This technology describes a new method for targeting solid tumors using gene therapy. More specifically, mammalian HEC-1 has a critical role in chromosome segregation and thus cell division. This technology involves targeted depletion of HEC-1 using shRNA against the HEC-1 mRNA inhibiting cancer cell growth in cell culture models (in vitro) as well as regressed tumor size in mouse model (in vivo). Additionally, this is the sole technology using an insect cell based recombinant adeno-associated virus (rAAV) gene transfer vehicle with high titer containing the shRNA of interest thus enabling high dosing during therapeutic intervention if necessary. This technology platform has the potential to treat a broad spectrum of cancers and related diseases. Applications: A new anti-cancer adjuvant therapy for non- resectable tumors targeting HEC-1 protein; A new method involving insect cell based production of recombinant adeno- associated virus (rAAV) gene transfer vehicle Market: 600,000 deaths from cancer related diseases estimated in 2006. The technology platform involving new cancer therapy and gene therapy technology has a potential market of more than 50 billion dollars. Development Status: The technology is currently in pre- clinical stage of development. Publications: 1. EN Gurzov et al., "RNA Interference against Hec 1 inhibits tumor growth in vivo," Gene Ther. 2006 Jan; 13 (1):1-7. 2. JG DeLuca et al., "Hec1 and nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites," Mol Biol Cell. 2005 Feb; 16 (2):519-531. 3. S Martin-Lluesma et al., "Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2," Science 2002 Sep 27; 297 (5590):2267-2270. 4. T Hori et al., "Dynamic behavior of Nuf2-Hec1 complex that localizes to the centrosome and centromere and is essential for mitotic progression in vertebrate cells," J Cell Sci. 2003 Aug 15; 116 (Pt 16):3347-3362. 5. Y Chen et al., "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is essential for faithful chromosome segregation," J Biol Chem. 2002 Dec 20; 277 (51):49408-49416.

Preclinical

U.S. Provisional Application No. 60/782,277 filed 15 Mar 2006 (HHS Reference No. E-200-2005/0-US-01) Inventors: Robert M. Kotin and Lina Li (NHLBI)

Licensees sought. Available for non-exclusive or exclusive licensing. Collaborative Research Opportunity: The National Heart, Lung, and Blood Institute, Laboratory of Biochemical Genetics, is seeking statements of capability or interest from parties interested in collaborative research to further develop therapeutics using rAAV-shRNA to induce selective cytotoxicity in primary and metastatic solid tumors. Partners are sought for conducting translational research from preclinical trials to clinical trials. Please contact Dr. Vincent Kolesnitchenko, Office of Technology Transfer and Development, NHLBI at 301-594-4115 or by e-mail (vk5q@nih.gov) for more information.