ALK as the Therapeutic Target for the Treatment of Proliferative, Vascular and Neurological Disorders Induced by Pleiotrophin
Reference #: 2000-023
This invention relates to the discovery that pleiotrophin (PTN) binds to and activates a pleiotrophin-receptor (ALK), which is responsible for the events associated with pleiotrophin activity including tumorigenesis, cell proliferation, and cell invasion. We have identified a specific region in the ALK (amino acid residues 368 to 447) which binds PTN (Ligand-binding domain, LBD). By interfering with that association, the cascade of events associated with pleiotrophin activity can be prevented or reversed. Either small molecule against LBD or anti-LBD ALK antibodies can be used as effective therapeutics against certain cancer and developmental disorders.
- Potential therapeutic for the treatment of cancers such as Glioblastoma multiforme, Pancreatic, Colon, Breast, Prostate, and Lung Cancer.
- Potential therapeutics for neurological and cardiovascular diseases.
- Promoting Wound healing
- Research tool
- Identified receptor can be used in diagnostics of pathological conditions
Targeting Ligand-binding domain of ALK offers specificity.
Stage of Development
High expression of ALK demonstrated in the serum of patients with different types of cancer (such as those listed above). Mouse monoclonal antibodies (IgGs) against the extracellular ligand binding site of PTN (LBD) in ALK inhibit tumor growth of ALK dependent tumors in mice such as pancreatic cancer. Similar data obtained using antisense molecule approach.
“Ribozyme targeting of the growth factor pleiotrophin in established tumors: a gene therapy approach”. Wellstein et al., Gene Therapy, 2005 Feb;12(4):339-46.
“Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types” Wellstein et al., JBC 2002 September 27;277(39):35990-8
“Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase”. Wellstein et al., J Biol Chem. 2002 Sep 27;277(39):35862-8.
“Serum levels of the angiogenic factor pleiotrophin in relation to disease stage in lung cancer patients”. Wellstein et al, Br J Cancer. 2002 Mar 18;86(6):858-63.
“Significance of the expression of the growth factor pleiotrophin in pancreatic cancer patients”. Wellstein et al., Clin Cancer Res. 2002 Mar;8(3):823-7.
Emma Bowden, Elena Tassi, Anton Wellstein
US Patent # 7528109 issued on 09/05/05. Corresponding US and foreign patent applications pending.