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Methods for Treating Chronic Lymphocytic Leukemia (CLL) by Regulating Cell Survival

技术优势

BAFF has been reported to be a potent regulator of normal B cell development and function and plays an important role in the resistance to apoptosis of malignant B cells, such as CLL, lymphoma, and myeloma cells. APRIL stimulates tumor cell growth as well as proliferation of primary lymphocytes and transgenic mice overexpressing APRIL develop a clonal expansion of B1 lymphocytes similar to that seen in CLL. Both BAFF and APRIL are highly expressed by “nurselike cells” (NLCs) in the blood microenvironment, promoting CLL-cell survival in a paracrine manner. Therefore, blocking leukemia-cell signaling induced BAFF and APRIL disrupt the support required by the leukemic cells. Induction of the pathways downstream of BAFF and APRIL lead to CLL-cell activation of the NF-kappa B1 and enhanced CLL-cell expression of the anti-apoptotic protein McH. Inhibition of these pathways leads to a specific reduction in CLL-cell survival without affecting viability of normal cells. SDF-1 alpha has an additive effect on the viability of isolated CLL cells cultured with BAFF and/or APRIL, indicating that BAFF or APRIL promote CLL cell survival via a distinct pathway(s) and that jointly targeting these pathways in CLL patients may result in improved response.

技术应用

Specific therapeutic induction of apoptosis of CLL-cells, through neutralizing BAFF or APRIL, such that an activity of BAFF or APRIL is inhibited. A method for detecting inhibitors of CLL and/or treating leukemias.

详细技术说明

Despite their longevity in vivo, CLL cells typically undergo spontaneous apoptosis under conditions that support the growth of normal human B cell lines in vitro. This implies that there are factors essential for survival that are not intrinsic to the CLL B cell, but contributed by additional cells in the blood microenvironment. This invention provides a method that distinguishes CLL from normal cells and specifically targets CLL cells for apoptosis through disruption of survival signals communicated between the leukemic cells and the local environment. This method comprises contacting the cell with an agent capable of reducing cell survival through inhibiting paracrine signaling between CLL cells and accessory cells acting through the B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL).

*Abstract

Existing therapies for CLL include chemotherapies such as fludarabine or chlorambucil, and antibody therapy such as ritiximab. Such therapies can be efficacious; however each have substantial side effects, including damage caused to normal tissue. Therefore, a therapeutic strategy is needed, which possesses the ability to kill cancerous cells directly, as is contemplated with the above chemotherapies and antibody therapy, while interrupting a cancerous cell survival factor from supporting cells.

*IP Issue Date

Dec 10, 2009

*Principal Investigation

Name: Tomoyuki Endo

Department:

Name: Thomas Kipps

Department:

Name: Mitsufumi Nishio

Department:

附加资料

Patent Number: US20090304614A1
Application Number: US200886596A
Inventor: Bordat, Pascal | Bordat, Pascal | Tarroux, Roger | Saurat, Jean-Hilaire | Sorg, Olivier | Daunes-Marion, Sylvie
Priority Date: 14 Dec 2005
Priority Number: US20090304614A1
Application Date: 28 Oct 2008
Publication Date: 10 Dec 2009
IPC Current: A61K000837 | A61K000834 | A61Q000508 | A61Q001902
US Class: 424062
Title: Use of Polyunsaturated Compounds as Whitening Agents
Usefulness: Use of Polyunsaturated Compounds as Whitening Agents
Summary: (I) is useful as bleaching agent and/or cleanser in the dermatological composition for hair and/or skin, particularly to depigment and eliminate aging spots on human skin (claimed). No biological data given.

主要类别

生物医学

细分类别

医疗化妆品

申请号码

20090304614

其他

State Of Development

This technology is offered exclusively or nonexclusively for U.S. and/or certain foreign countries. A commercial sponsor for potential future research is sought.

Related Materials

Thomas J. Kipps, publication WO/2006/116366.

Tech ID/UC Case

19548/2005-221-0

Related Cases

2005-221-0

国家/地区

美国