NON-HUMAN TRANSGENIC MAMMALIAN ANIMAL EXPRESSING HUMAN EGFR SPECIFICALLY IN LUNGS
|Posted date||Mar 29, 2017|
|International application number||2016JP073053|
|International publication number||WO 2017026383|
|Date of international filing||Aug 5, 2016|
|Date of international publication||Feb 16, 2017|
|Title||NON-HUMAN TRANSGENIC MAMMALIAN ANIMAL EXPRESSING HUMAN EGFR SPECIFICALLY IN LUNGS|
[Problem] To provide transgenic mice in which h-EGFR is expressed specifically in the lungs, and which spontaneously develop lung cancer.
[Solution] A non-human transgenic mammalian animal (specifically, a transgenic mouse) in which a human [L858R] epidermal growth factor receptor ([L858R]-h-EGFR) gene, which includes an entire genetic region of 28 exons and 27 introns, is inserted downstream of the expression promoter region thereof. When doing so, it is preferable that the expression promoter region includes a tetracycline response element (TRE), and that the non-human transgenic mammal has a reverse tetracycline-controlled transactivator (rtTA) gene inserted downstream of the expression promoter of the lung-specific expression gene in the mammal.
|Outline of related art and contending technology||
Lung cancer is, malignant tumor occurring in the lung. When the lung cancer is found, often already made in the corresponding, known as refractory disease. In Japan, the number of lung cancer deaths, in various tumor within a patient at 1 men, 3 women at position occupies the second position. As the type of lung cancer, small cell lung cancer is of the entire 20%, 80% in non-small cell lung cancer. As a therapy for small cell lung cancer among these, in the case of stage Ia, surgery or radiation therapy is, in the case of subsequent, chemotherapeutic (anti-cancer agent) is used. In addition, as a method of treating non-small cell lung, in the case of surgical treatment to stage III is, in the case of a subsequent, chemical therapy is used. In recent years, non-small cell lung cancer as a chemotherapy drug, molecular target therapeutic agent (for example, EGFR tyrosine kinase inhibitors, anti-vascular endothelial cell growth factor and the like) is used. The therapeutic agent is a molecular target, a high initial administration effect. However, a long period of use, a cancer cell resistance occurs, it may become impossible to effect is noted. Current, drug resistance of cancer cells being conducted research, the mechanism is not fully elucidated.
Among all lung cancer, about half of the h-EGFR gene mutations is observed. H-EGFR is, in the lipid bilayer membrane protein, recognizes the epidermal growth factor (EGF) receptor signal transduction. Usually, h-EGFR is activated by EGF and, h-EGFR tyrosine kinase activity is enhanced has, in the self-phosphorylation, as a variety of normal response to exert an action of cell growth. However, the patient's lung cancer gene mutation was h-EGFR in many cases. H-EGFR patient as found in wild type, L858R (858 leucine and was mutated to arginine), T790M (790 position was mutated to methionine as sureoinin), ΔE749-A750(749 glutamic acid and alanine in position 750 and deficient) and the like are known. (Ex21) The second exon of these 21 mutant derived from L858R is located, seen in about 40% -45% of the lung. The mutations h-EGFR([L858R]-h-EGFR) is, even in the state where there is no EGF, tyrosine kinase activity is enhanced, autophosphorylation occurs, causing excessive cell proliferation. For this reason, L858R: and - h-EGFR mice having TG, research is being performed to the property (non-patent document 1, 2). In addition, the second (Ex20) to T790M exon 20: mutation is a h-EGFR, EGFR tyrosine kinase inhibitors having resistance becomes.
|IPC(International Patent Classification)|
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
Contact Information for " NON-HUMAN TRANSGENIC MAMMALIAN ANIMAL EXPRESSING HUMAN EGFR SPECIFICALLY IN LUNGS "
- Mie University Intellectual Property Office
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