title: Anti-CD44 mAb for the treatment of B-cell chronic lymphocytic leukemia and other hematological malignancies: evaluation of WO2013063498.
abstract: BACKGROUND
  The CD44 transmembrane glycoprotein family mediates cellular responses to the microenvironment through binding of hyaluronic acid (HA) and other proteins of the extracellular matrix. These interactions start intracellular signaling cascades that foster tumor growth, survival and spread.
  
  
  METHODS
  The patent concerns the use of a humanized anti-CD44 mAb (RG7356) to treat patients with aggressive forms of chronic lymphocytic leukemia (CLL). The RG7356 humanized antibody was designed to bind the constant region of CD44, preventing binding with HA. The interruption of this circuit in vitro is followed by the induction of caspase-dependent apoptosis in leukemic cells. In agreement with a functional association between CD44 and zeta-associated protein of 70 kDa (ZAP-70) in activating intracellular signaling, the strongest effects were observed in ZAP-70(+) CLL cells, generally associated to a poor prognosis. Furthermore, these effects were confirmed using in vivo models, where CLL cells were xenografted in immunocompromised mice.
  
  
  CONCLUSIONS
  In summary, these studies suggest that this new humanized mAb may provide additional clinical benefit to CLL patients receiving current standard treatments, specifically to those with a more aggressive disease.
authors.affiliation: IRCCS "Centro di Riferimento Oncologico della Basilicata", Hematology Oncology Department , 85028 Rionero in Vulture , Italy +39 0972 726521 ; +39 0972 726217 ; giovannidarena@libero.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Calapai
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects* / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D010330:Patents as Topic
chemical_list: D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors
keywords: CD44; chronic lymphocytic leukemia; mAbs; targeted therapies