【摘要】： LM-1蛋白質(zhì)與白細(xì)胞的遷移和粘附密切相關(guān),它表達(dá)在白細(xì)胞表面,通過與其配體結(jié)合,以介導(dǎo)白細(xì)胞從血液循環(huán)中進(jìn)入腸道和中樞神經(jīng)系統(tǒng),LM-1的功能的異�？梢詫�(dǎo)致腸道系統(tǒng)的慢性炎癥和中樞神經(jīng)系統(tǒng)損傷,從而引起一系列人類自身免疫疾病如asthma,arthritis,Crohn's disease,IBD和MS等。目前,眾多國際上知名的醫(yī)藥公司正在開發(fā)以LM-1蛋白質(zhì)為靶標(biāo)的藥物,目前唯一的一個以LM-1蛋白質(zhì)為靶標(biāo)的抗體藥物會同時抑制活化和未活化的LM-1的功能,因此,該藥物具有較大的副作用。我們的研究應(yīng)用噬菌體展示技術(shù),以活化狀態(tài)的LM-1為抗原,篩選出了抗LM-1蛋白質(zhì)的陽性噬菌體,純化了表達(dá)于陽性噬菌體表面的scFV,用FACS和Flow Chamber系統(tǒng)鑒定后證明此scFV能特異性抗活化狀態(tài)LM-1蛋白質(zhì)并且具有非常高的效價。這就為進(jìn)一步開發(fā)以活化狀態(tài)的LM-1為靶標(biāo)的抗體藥物提供了基礎(chǔ),相比于上市的不能區(qū)分活化和未活化的LM-1蛋白質(zhì)的抗體藥物,我們的抗體具有明顯的優(yōu)勢,由于能將藥物靶向運輸?shù)侥け砻娲嬖诨罨癄顟B(tài)LM-1的細(xì)胞,特異性對病變細(xì)胞進(jìn)行殺傷,從而能保護(hù)正常的細(xì)胞,能顯著的降低藥物的副作用,具有非常好的應(yīng)用前景。
[Abstract]:LM-1 protein is closely related to leukocyte migration and adhesion. It is expressed on the surface of white blood cells, and by binding with its ligand, it mediates leukocytes from blood circulation to the intestine and central nervous system. The abnormal function of LM-1 can lead to chronic inflammation of the intestinal system and damage of the central nervous system, resulting in a series of autoimmune diseases such as asthma,arthritis,Crohn's disease,IBD and MS. At present, many internationally renowned pharmaceutical companies are developing drugs targeting LM-1 protein. The only antibody drug targeting LM-1 protein will inhibit the function of activated and unactivated LM-1 at the same time. The drug has great side effects. Using phage display technique and activated LM-1 as antigen, we screened out the positive phage against LM-1 protein and purified scFV, expressed on the surface of positive phage. FACS and Flow Chamber analysis showed that the scFV could specifically resist the activated LM-1 protein and had a very high titer. This provides a basis for the further development of antibody drugs targeting activated LM-1, and our antibodies have obvious advantages over those that do not distinguish between activated and unactivated LM-1 proteins on the market. Because the drug can be targeted to the surface of the membrane there are activated LM-1 cells, the specific killing of pathological cells, thus can protect the normal cells, can significantly reduce the side effects of drugs, has a very good application prospects.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R392

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