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Immunotherapy for the treatment of cancer

A technology that regulates immunity and immune checkpoints, applied in the direction of immunoglobulin, antibody medical components, chemical instruments and methods, etc., to achieve the effect of inhibiting tumor growth and broadening efficacy

Pending Publication Date: 2021-10-22
塔尔格免疫治疗有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Despite encouraging initial results, the development of immunotherapies for cancer remains a major challenge for tumor immunologists

Method used

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  • Immunotherapy for the treatment of cancer
  • Immunotherapy for the treatment of cancer
  • Immunotherapy for the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0239] Example 1 - Effect of PEI-PEG-EGF / polyIC alone

[0240] A431, U87 and MCF7 cells (40,000 cells per well) were treated with various concentrations (0.125, 0.25, 0.5, 1 μg / ml) of PEI-PEG-EGF / polyIC for 5 hours.

[0241] Human IP-10 (CXCL10) secretion was quantified by ELISA assay (ABTS ELISA Development Kit, Peprotech). IP10 secretion was strongly increased in A431 cells expressing high EGFR levels after incubation with PEI-PEG-EGF / polyIC for 5 hours ( figure 1 ).

[0242] A431 cells were treated with PEI-PEG-EGF / polyIC at a concentration of 0.125 μg / ml for 5 hours. A431 cells were then stained with a PD-L1-PE-labeled antibody (Biolegend, Cat. No. 393607) in PBS with 2% FCS for 40 minutes on ice, washed and analyzed by FACS instrument. PD-L1 expression was significantly increased after PEI-PEG-EGF / polyIC treatment (MFI=751 ) compared to untreated control cells (MFI=431 ). An isotype control was used as a negative control (MFI=13).

[0243] After PEI-PEG-EGF / polyIC t...

example 2

[0246] Example 2 - In Vitro Effect of PEI-PEG-EGF / polyIC in Combination with Immunomodulatory Therapies Nivolumab and 4-1BB Antibody

[0247]Nivolumab: 40.000 A431 cells were treated with PEI-PEG-EGF / polyIC at concentrations of 0.125, 0.25, 0.5, 1 μg / ml for 5 hours. 200.000 PBMC were then stimulated with CD3 (5 μg / ml) and treated with diluted medium containing PEI-PEG-EGF / polyIC (0.125 μg / ml) alone or in combination with nivolumab (20 μg / ml) (1:2) to attack for 48 hours. After 48 hours, media from challenged PBMCs were collected and INFy production was measured by ELISA assay ( image 3 ).

[0248] Combining PEI-PEG-EGF / polyIC with nivolumab significantly increased IFN-γ production by PBMCs ( image 3 ).

[0249] Antibody 4-1BB: 40.000 A431 cells were treated with PEI-PEG-EGF / polyIC at a concentration of 0.5 μg / ml for 5 hours. 200,000 PBMCs from healthy donors were stimulated or unstimulated with CD3 (0.5 μg / ml) and compared with PEI-PEG-EGF / polyIC alone or with 4-1BB (Biol...

example 3

[0253] Example 3 - In vivo efficacy of the combination of PEI-PEG-mEGF / polyIC+anti-PD-1

[0254] The effect of PEI-PEG-EGF / polyIC+anti-PD-1 on RencaEGFR lung metastasis in immunocompetent mice was examined.

[0255] Materials and methods: cells: RencaEGFR; polyplex PEI-PEG-EGF / polyIC and -LPEI / EGF mice: 1 / 0.75); poly IC from Dalton; HBG (Hepes buffered glucose), N / P:8. Anti-PD-1: rat IgG2a, kappa anti-mouse PD-1 antibody (Bioxcell clone RMP1-14).

[0256] 250,000 RencaEGFR cells were injected intravenously into 40 Balb / c immunocompetent female mice (6 weeks old, weight: 18-21 gr) to induce RencaEGFR tumor formation in the lung. After 10 days, the animals were divided into 4 groups, 10 animals / group (untreated (UT), anti-PD-1, PEI-PEG-EGF / polyIC and PEI-PEG-EGF / polyIC+aPD1 (anti-PD -1).

[0257] Mice bearing RencaEGFR tumors were treated with PEI-PEG-EGF / polyIC alone at 250 μg / kg, 6 injections / week intravenously for 2 weeks, or with anti-PD-1 (RPM1-14, rat IgG2a, Biox cell...

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Abstract

The present invention relates to a kit-of-parts comprising and a composition comprising a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate comprising a polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties and one or more targeting moieties, and wherein each of said one or more targeting moieties is capable of binding to a cancer antigen; and at least one antibody, wherein said at least one antibody is capable of modulating an immune checkpoint protein. Further the invention relates to this composition or kit-of-parts for use in the treatment of cancer.

Description

[0001] The present invention relates to the field of immunotherapeutic cancer treatment. In particular, the present invention relates to a kit and a composition comprising: a polyplex comprising a double-stranded RNA (dsRNA) and a polymeric conjugate comprising polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties, and one or more targeting moieties, and wherein the one or more Each of the targeting moieties is capable of binding a cancer antigen; and at least one antibody, wherein the at least one antibody is capable of modulating an immune checkpoint protein. Further, the present invention relates to such compositions or kits for use in the treatment of cancer. Background technique [0002] Antibodies targeting tumor-associated antigens have become an important therapeutic modality for malignancies. Several monoclonal antibodies (mAbs) have been shown to be relatively well tolerated and effective for the treatment of many different malignancies. Although...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K47/60A61K47/59A61P35/00A61K31/715
CPCC07K17/06A61P35/00A61K39/39558A61K2039/505C07K16/32C07K16/2818C07K2318/20C07K16/2878A61K31/713A61K47/59A61K47/642A61K47/64A61K47/646A61K2300/00A61K47/60
Inventor D·布洛卡D·可莱克希亚L·德’阿米科E·基塔斯A·列维茨基E·波博-维勒A·希尔M·齐格勒D·巴吉奇A·贾兹宾
Owner 塔尔格免疫治疗有限公司
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