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New Activity of HSP90 Inhibitors Inducing Down Regulation of ZAP-70 and Inducing Apoptosis in Leukemia Cells

技术优势

This invention provides the first evidence that Hsp90 plays an active role in CLL progression/prognosis. Inhibiting Hsp90 or ZAP-70 activity or disrupting the interaction between the two molecules directs otherwise resistant cells to undergo apoptosis. Hsp90 inhibitors (proprietary or those available in the art) can induce cancer cell apoptosis through the directed down regulation of ZAP-70. Hsp90 inhibition leads to the specific down regulation of pathological ZAP-70 in leukemic cells without down regulating ZAP-70 in natural killer cells or healthy T-cells.

技术应用

A method and compositions useful to modulate apoptosis in a cell. Treatment of patients with CLL or other cell proliferative disorders. Prophylaxis in patients with high risk to develop leukemias. Determination of cancer risk factors and biological analysis of important signaling pathways in leukemia. A method for the identification of novel Hsp90 “client” proteins. A method for early diagnosis of CLL and other cancers. In vitro test that can be used as a clinical prognostic factor, based upon the detection of active Hsp90 complexes and the induction of apoptosis. This prognostic assay is amenable to high throughput automatization and could be applied to other types of normal or malignant cells.

详细技术说明

This invention provides new uses of specific inhibitors of heat shock protein 90 (Hsp90) to induce apoptosis of leukemic cells. Additionally, this technology provides a clinical prognostic marker in cancer cells, based on the detection of apoptosis in vitro and the identification of active Hsp90 complexes.

*Abstract

Cancer is in part a result of the ability of pathologically altered cells to evade apoptosis. Therefore, there is a need to identify compounds that can key regulate the key interactions between proteins involved in apoptotic regulation in order to treat cancer. ZAP-70 is considered the best prognostic factor for disease progression and is correlated with poor clinical outcome in CLL patients, in part through its ability to serve an anti-apoptotic function in these cells. A compound with the ability to down regulate ZAP-70 and induce apoptosis specifically in CLL cells would provide an invaluable therapy for patients with aggressive disease.

*IP Issue Date

Jun 3, 2014

*Principal Investigation

Name: Francis Burrows

Department:

Name: Januario Castro

Department:

Name: Adeela Kamal

Department:

Name: Thomas Kipps

Department:

Name: Carlos Prada

Department:

附加资料

Patent Number: US8741578B2
Application Number: US2007666899A
Inventor: Castro, Januario E. | Kipps, Thomas J. | Prada, Carlos E.
Priority Date: 2 Nov 2004
Priority Number: US8741578B2
Application Date: 4 Oct 2007
Publication Date: 3 Jun 2014
IPC Current: G01N003353 | G01N0033574
US Class: 4350071 | 43500721 | 43500723
Assignee Applicant: The Regents of the University of California
Title: Methods of detecting chronic lymphocytic leukemia with Hsp90 and ZAP-70
Usefulness: Methods of detecting chronic lymphocytic leukemia with Hsp90 and ZAP-70
Summary: (M1) is useful for determining the prognosis or diagnosis of a subject at risk for a cell proliferative disorder such as leukemia, where the subject is a mammal, preferably a human. (M2) is useful for detecting chronic lymphocytic leukemia (CLL). (M3) is useful for modulating apoptosis in a cell, preferably neoplastic cell. (M4) is useful for treating leukemia, preferably CLL in a subject (claimed).
Novelty: Determining prognosis/diagnosis of subject at risk for cell proliferative disorder, involves determining presence of heat shock protein 90-Zeta associated protein-70 complex and/or amount of activated Hsp90 in cell expressing ZAP-70

主要类别

诊断/治疗

细分类别

癌症/肿瘤

申请号码

8741578

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

Tech ID/UC Case

19596/2005-094-0

Related Cases

2005-094-0

国家/地区

美国