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Combined treatment with netrin-1 interfering drug and immune checkpoint inhibitor drugs

An immune checkpoint and inhibitor technology, applied in drug combinations, immunoglobulins, anti-growth factor immunoglobulins, etc., can solve problems such as unclear cellular immunogenicity

Pending Publication Date: 2019-09-27
НЕТРИ ФАРМА +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is unclear whether netrin-1 interference-induced cell death is immunogenic

Method used

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  • Combined treatment with netrin-1 interfering drug and immune checkpoint inhibitor drugs
  • Combined treatment with netrin-1 interfering drug and immune checkpoint inhibitor drugs
  • Combined treatment with netrin-1 interfering drug and immune checkpoint inhibitor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0148] Materials and methods

[0149] cell line:

[0150] mouse breast cancer EMT6 ( CRL2755 TM - LGC standard - France) cells were cultured in Eagle's minimum essential medium supplemented with 10% fetal bovine serum and antibiotics (streptomycin and penicillin).

[0151] Mus musculus (Mus Musculus) mammary gland 4T1 ( CRL2539 TM - LGC Standard - France) cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM), 10% FBS.

[0152] Mouse experiments:

[0153] Mice were maintained in a specific pathogen-free animal facility and handled according to institutional guidelines and protocols approved by the Animal Care and Use Committee (Leon Berard Center Joint Evaluation Committee, ENS Transit Animals, PBES and P4 Laboratories; CECCAP ).

[0154] Will 5.10 5 or 10.10 5EMT6 cells were transplanted subcutaneously into the flanks of BalbC / J 8-week-old female mice. On days 7, 11 and 14, all animals were treated 3 times with 400 μg / injection of anti-CTLA4 (BioX ...

Embodiment 2

[0170] Will 5.10 5 E0771 cells were transplanted subcutaneously into the flank of C57b6J 8-week-old female mice. Six days after transplantation, animals were randomly divided into 4 groups and treated with NP137 or NP001 IgG1 control isotypes alone or in combination with anti-PD-1 antibody. All animals were treated twice weekly with 20 mg / Kg of anti-CTLA4 (BioX cells-clone 9H10) and / or 10 mg / Kg of NP antibody by IP route. Tumor volumes were measured twice a week by external calipers. When the tumor reaches 2000mm 3 When the volume was reached, the mice were sacrificed.

[0171] Will 5.10 5 MC38 cells were transplanted subcutaneously into the flank of C57b6J 8-week-old female mice. Six days after transplantation, animals were randomly divided into 4 groups and treated with NP137 or NP001 IgG1 control isotypes alone or in combination with anti-PD-1 antibody. All animals were treated twice weekly with 5 mg / Kg of anti-PD1 (BioX cell-clone RMP1-14) and / or 10 mg / Kg of NP antib...

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Abstract

The invention provides the combination or combined use of (i) a compound able to disrupt or impede netrin-1 / netrin-1 receptors interaction or netrin-1-mediated receptor dimerization, also called herein a NTN1 neutralizing agent, which compound may be an antibody binding to netrin-1 or anti-netrin-1 antibody, and (ii) an immune checkpoint inhibitor, in the treatment of cancer. The composition may comprise an anti-netrin-1 antibody and an immune checkpoint inhibitor, for use as an anticancerous drug with a simultaneous, separate or sequential administration of the anti-netrin-1 antibody and the immune checkpoint inhibitor to a patient.

Description

technical field [0001] The present invention relates to novel combination compositions and methods for the treatment of cancer. Background technique [0002] The axon guidance protein netrin-1 (Netrin-1) is a soluble protein thought to play a key role in cancer progression by regulating programmed cell death. [0003] Indeed, netrin-1 receptors such as DCC and UNC5H (ie UNC5H1, UNC5H2, UNC5H3 and UNC5H4 also known as UNC5A, UNC5B, UNC5C or UNC5D) - belong to the family of so-called dependency receptors. These transmembrane receptors act in two opposite ways: they induce positive signaling leading to cell proliferation, survival and differentiation in the presence of their ligand netrin-1. In the absence of netrin-1, these receptors, when unbound, transduce negative signaling that initiates apoptosis. After ligand withdrawal, cell death-induced signaling pathways require the interaction and cleavage of specific apical caspases. As a result, mutation of the caspase site in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/22C07K16/28C07K16/30A61K39/00
CPCA61K2039/507A61P35/00C07K16/22C07K16/2818C07K16/30C07K2317/565C07K2317/76A61K2300/00A61K39/395
Inventor 邦雅曼·迪卡鲁热达维德·戈德施奈德安娜·玛丽亚·丽塔·雷达维德邦雅曼·吉贝尔帕特里克·梅伦
Owner НЕТРИ ФАРМА
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