Combination therapies for treating cancers

一种癌症、疗法的技术，应用在治疗癌症的疗法和组合物领域

Inactive Publication Date: 2017-09-26
GILEAD SCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, some Bcl-2 inhibitors can cause thrombocytopenia and have limited use in clinical treatment (see, eg, Zhang et al., Cell Death and Differentiation 14:943-951, 2007)

Method used

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  • Combination therapies for treating cancers
  • Combination therapies for treating cancers
  • Combination therapies for treating cancers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0246] Example 1: Human CLL Apoptosis Test

[0247] Peripheral blood mononuclear cells (PBMC) were isolated from patients with primary chronic lymphocytic leukemia (CLL), and cultured in lymphocyte growth medium (LGM, RPMI 1640, 1mM sodium pyruvate, 10mM HEPES, pH 7.4, 100U / mL penicillin / 100 μg / mL streptomycin, 55 μM β-mercaptoethanol, 2 mM GlutaMAX, and 10% FBS) at 37 °C with 5% CO 2 Incubate for 3-5 hours. Cells were then centrifuged for 10 min at room temperature and resuspended in an appropriate volume of LGM for plating (maximum cell density = 3.12 X 10 6 / ml). With HS-5 co-cultures (prior to assay, plate at 37°C with 3×10 in 100 μl 4 HS-5 cells were plated overnight) or final assay wells were set in U-bottom 96-well tissue culture plates without co-culture.

[0248] Cell suspension (80 μL, 2.5×10 5 –9.4×10 4 ) were added to the plate and incubated for 1 hour, then stimulated with αIgM / αIgG (7.8 μg / well) and αCD40 (4 μg / well). Cells were incubated with compounds f...

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Abstract

Provided herein are methods that relate to a therapeutic strategy for treatment of cancer, including hematological malignancies. In particular, the methods include administration entospletinib and a Bcl-2 inhibitor, such as venetoclax, navitoclax, and ABT-737.

Description

technical field [0001] The present invention relates generally to therapies and compositions for the treatment of cancer, and more particularly to the use of spleen tyrosine kinase (Syk) inhibitors in combination with B-cell CLL / lymphoma 2 (Bcl-2) inhibitors for the treatment of cancer. Background technique [0002] Syk inhibitors useful as anticancer agents include entospletinib, which is in Phase 2Trial of Entospletinib (GS-9973), a Selective SYK Inhibitor, in Follicular Lymphoma (FL), Sharman et al., Blood, 124(21), Dec.6 , discussed in 2014. [0003] Various compounds that inhibit the activity of anti-apoptotic Bcl proteins are known in the art. A variety of Bcl-2-selective apoptosis-inducing compounds are useful in the treatment of cancer. However, some Bcl-2 inhibitors can cause thrombocytopenia and have limited use in clinical treatment (see eg, Zhang et al., Cell Death and Differentiation 14:943-951, 2007). Accordingly, there remains a need for alternative therapi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/437A61K31/496A61K31/5377A61P35/00A61P35/02
CPCA61K31/437A61K31/496A61K31/5377A61K2300/00A61K31/495A61P35/00A61K31/4985
Inventor J.A.迪保罗R.M.琼斯D.B.图马斯
Owner GILEAD SCI INC
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