Inhibitory oligonucleotides for treating tumors

An oligonucleotide and inhibitor technology, applied in the field of inhibitory oligonucleotides used to treat tumors, can solve problems such as undesired immune response

Inactive Publication Date: 2017-02-22
SBI BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] However, immune responses can sometimes be unwanted and cause immune-mediated disorders, including autoimmune diseases, transplant rejection, hypersensitivity reactions, diseases associated with microbial overstimulation of the host's immune system, and Toll-like receptors ( TLR)-mediated diseases

Method used

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  • Inhibitory oligonucleotides for treating tumors
  • Inhibitory oligonucleotides for treating tumors
  • Inhibitory oligonucleotides for treating tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0286] Confirmation of diffuse large B-cell lymphoma (DLBCL) by sequencing in the presence of the MYD88 L265P mutant cell line

[0287] experimental method

[0288]OCI-Ly3.3 with MYD88 L265P mutant and MYD88 wild-type OCI-Ly19 were cultured in Iscove's modified Dulbecco's medium (IMDM, Hyclone , Logan, UT, USA). All cells were maintained at 37°C in 5% CO2 under humidified conditions. Using Genomic DNA Kit (TransGen Biotech Co.Beijing, China) from 3 × 10 6 Cellular DNA was extracted from OCI-Ly3.3 or OCI-Ly19 cells, and Tks Gflex DNA polymerase (Takara Biotechnology, Dalian, China) and MYD 88 forward primer (5'-GTTGAAGACTGGGCTTGTCC-3', SEQ ID NO.: 51) and reverse primer (5'-AGGAGGCAGGGCAGAAGTA-3', SEQ ID NO.:52) for polymerase chain reaction (PCR). PCR products were extracted by gel extraction kit (Kangwei Biotechnology, Beijing, China), and cloned into pEasy-Blunt cloning kit (TransGen Biotech Co. Beijing, China). Two clones from each cell line were selected for seq...

Embodiment 2

[0292] Effects of TLR7 / TLR9 antagonists on ABC-DLBCL cells with MYD88 L265P mutant

[0293] experimental method

[0294] In order to observe the inhibitory effect of TLR7 / 9 antagonists on the proliferation of ABC-DLBCL cells, 5 x 10 cells in 96-well plates were cultured with TLR7 / TLR9 antagonists in the dose range specified below. 5 / well of OCI-Ly3.3 and OCI-Ly19 cells. Cell viability was measured using a tetrazolium salt based assay (WST-1 ) purchased from Beyotime Institute of Biotechnology (Jiangsu, China). The percentage of viable cells was calculated as the ratio of the absorbance of treated cells to the absorbance of control cells at 450 nm.

[0295] To investigate cytokine secretion from DLBCL cells using TLR7 / TLR9 antagonists, 2x10 5 OCI-Ly19 or OCI-Ly 3.3 cells per well with TLR7 / 9 antagonist (CCT) at concentrations indicated below 8 , (CCT) 12 and (CCT) 12-M (Sequence IDs corresponding to NO.20, 12 and 43, respectively) were incubated together. The cytoki...

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Abstract

A method for treating B-cell lymphoma in a subject that has been diagnosed as having a B-cell lymphoma characterized by a mutation in MYD88 and is in need of such treatment is presented. The lymphoma is treated with an oligonucleotide having a sequence 5'-(CCT)n-3'. The B-cell lymphoma may be activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) or Waldenstrom's macroglobulinemia (WM).

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit and priority of US Provisional Patent Application Serial No. 61 / 937,376, filed February 7, 2014, the entire contents of which are hereby incorporated by reference in their entirety. [0003] field of invention [0004] The present invention relates to oligonucleotides and uses thereof for the treatment of tumors such as B cell lymphoma. [0005] Background of the invention [0006] The immune system protects the body against bacterial, parasite, fungal, viral infections and prevents the growth of tumor cells. Immunity can be classified as innate immunity and adaptive immunity. The innate immune response usually occurs immediately after infection to provide an early barrier to infectious disease, while the adaptive immune response occurs later to generate antigen-specific long-term protective immunity. [0007] However, immune responses can sometimes be unwanted and cause immune-media...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K38/00C07H21/02
CPCA61K31/713A61K45/06A61P35/02A61P43/00C12N15/117C12N2310/17C12N2310/315C12N2320/31
Inventor 钱大鹏江指永二
Owner SBI BIOTECH CO LTD
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