New Drug Treatment for Large B-Cell Lymphomas or Other Hematopoietic Malignancies

Addressing the need for new treatment options for the patients with indolent lymphomas, UC San Diego researchers have developed a new method to detect and treat lymphomas, including forms of non-Hodgkin lymphoma, based on targeting tumor necrosis factor-alpha signaling (TNF-alpha; a multifunctional pro-inflammatory cytokine). This technology is focused on providing new treatment methods for the group of lymphoma patients characterized as resistant to conventional treatment. Specifically, this technology provides a means for: (a) detecting altered expression of microRNAs (i.e. miR21, miR155), phosphatase and tensin homolog deleted on chromosome ten (PTEN), and SH2-containing inositol phosphatase (SHIP-1; enzyme that hydrolyzes inositol 1,4,5-triphosphate) characteristic of hematopoietic malignancies; and (b) administering an effective amount of proven TNF-alpha inhibitors (i.e., neutralizing anti-TNF-alpha antibodies or soluble TNF-alpha receptor). The differential expression of a miR155 and SHIP-1 may provide a means to identify lymphoma patients that have a poor prognosis or will respond to treatment with a TNF-alpha inhibitor.

Patent Number: US20110123524A1
Application Number: US2010919708A
Inventor: David, Michael | Pedersen, Irene Munk
Priority Date: 28 Jan 2008
Priority Number: US20110123524A1
Application Date: 2 Feb 2011
Publication Date: 26 May 2011
IPC Current: A61K0039395 | A61K003817 | A61P003500 | A61P003502
US Class: 4241331 | 4241421 | 4241581 | 5140193 | 5140196
Title: METHODS FOR TREATING HEMATOPOIETIC MALIGNANCIES
Usefulness: METHODS FOR TREATING HEMATOPOIETIC MALIGNANCIES
Summary: The methods are useful for treating a hematopoietic neoplasm in a mammalian subject. The hematopoietic neoplasm is a leukemia or a lymphoma. The lymphoma is a non-Hodgkin's lymphoma. The non-Hodgkin's lymphoma is a diffuse large B-cell lymphoma (DLBCL) of an activated B-cell (ABC) subtype (all claimed). Leukemia comprises acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and hairy cell leukemia.
Novelty: Treating a hematopoietic neoplasm, e.g. leukemia or lymphoma, in a mammalian subject by administering to the mammalian subject an amount of a tumor necrosis factor (TNF)-alpha inhibitor

Disease Diagnostic/Treatment

Cancer/Tumor

8883155

State Of Development

The inventors recorded elevated levels of miR-155 and consequent diminished SHIP-1 expression in diffuse large B cell lymphoma (DLBCL) that are the result of autocrine stimulation by the pro-inflammatory cytokine tumor necrosis factor (TNF). Standard anti-TNF regimens were sufficient to reduce miR-155 levels and restored SHIP-1 expression in DLBCL cells with an accompanying reduction in cell proliferation. This finding suggests that cytokine-regulated miRs may be a crucial link between inflammation and cancer and supports the feasibility of anti-TNF therapy as a novel and accessible treatment for DLBCL.

Related Materials

• An international patent application was filed on 22-Jan-2009 and published 06-Aug-2009 (Doc No. 2009097095). Consult this document for a detailed description of this offered technology.
• Pedersen IM, Otero D, Kao E, Miletic AV, Hother C, Ralfkiaer E, Rickert RC, Gronbaek K, David M. Onco-miR-155 targets SHIP1 to Promote TNF-Alpha-Dependent Growth of B Cell Lymphomas. EMBO Mol Med. 2009 Aug;1(5):288-95.

Additional Technologies by these Inventors

• Polyclonal Antibodies to IRF3

Tech ID/UC Case

20873/2008-071-0

Related Cases

2008-071-0

USA

Desktop View