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研究生:黃柏誠
研究生(外文):Bo-cheng Huang
論文名稱:探討蛋白酶促進抗體藥物活性之機制以增進其療效
論文名稱(外文):To investigate the mechanism of protease-enhanced antibody activity to increase its therapeutic efficacy
指導教授:鄭添祿
指導教授(外文):Tian-Lu Cheng
學位類別:碩士
校院名稱:國立中山大學
系所名稱:生物醫學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:61
中文關鍵詞:單株抗體標靶治療自體免疫疾病癌症藥物專一性
外文關鍵詞:Monoclonal antibodyspecificityCancerAutoimmune diseaseTargeted therapy
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當今單株抗體在臨床上已廣泛成為多種疾病的治療藥物,根據2010年 的藥物使用數據統計,標靶抗體藥物主要應用在腫瘤及癌症治療,其次為自體免疫疾病、發炎以及眾多傳染性疾病等等,且在單株抗體的銷售額經由市場統計也被指出,於2010年全球標靶抗體藥物的總銷售額高達430億美元,其中更有幾株標靶抗體的單一銷售便創造出高於10億元美元的驚人市場,包含大腸、直腸癌抗體藥ERBITUX®(Cetuximab)、乳癌抗體藥HERCEPTIN®(Trastuzumab)、類風濕性關節炎抗體藥物REMICADE®(Infliximab)及HUMIRA® (Adalimumab)等的治療性抗體藥物;在過去20年內,單株抗體治療在腫瘤醫學上已有許多成功的例子,足以成為醫療界的大宗藥物乃憑藉抗體自身對其抗原的專一性以及對其抗原作用之間的親和力,進而結合至抗原以阻斷由抗原傳遞的細胞訊息調控,達到抑制癌症或其他發炎疾病的蔓延,單株抗體治療在醫學上的突破與成功,使至今許多研究仍致力於尋找出疾病中可做為標靶治療的標誌以造福更多疾病患者,並且有更多臨床治療是以抗體藥物搭配傳統的化學療法、放射線療法或是其他小分子藥物,更有效率抑制癌細胞擴散提升抗癌的療效,由此可見單株抗體的研發創新在未來的醫療發展具備了十足的潛力性。
Monoclonal antibody has become clinical medicine of a variety of disease widely. According to the statistics of drug use, monoclonal antibody therapies apply to cancer, autoimmune diseases, inflammation and many infectious diseases, etc. And through the market statistics point out the sales of monoclonal antibodies is up to $ 43 billion in the market of global antibody drug in 2010. Moreover single sales target several strains of antibodies will create more than $ 1 billion sales, including Colorectal cancer drug, ERBITUX® (Cetuximab)、breast cancer drug HERCEPTIN® (Trastuzumab)、rheumatoid arthritis drug REMICADE® (Infliximab) and HUMIRA® (Adalimumab) , etc. Over the past 20 years, monoclonal antibody therapy in cancer medicine has many successful examples, and become a staple of drugs in the medical profession base on the binding-specificity between antibody and antigen in order to block the cell pathway for inhibiting tumor growth or other disease. Monoclonal antibody therapy on medical breakthroughs and success promote many studies are still committed to finding out the diseases targeted therapy can be used as a sign of disease in order to benefit more patients, and more clinical treatment is combination of antibody with traditional chemotherapy drugs, radiation therapy, or other small molecule drugs for more effective inhibition of cancer cell proliferation to enhance the therapeutic efficacy. Thus the development of innovative monoclonal antibody has the full potential in future.
論文審定書…………………………………………………………….. i
致謝…………………………………………………………………….. ii
中文摘要……………………………………………………………….. iii
英文摘要……………………………………………………………….. iv
第一章、研究背景與目的…………………………………………….. 1
第二章、研究材料及方法…………………………………………….. 5
第三章、研究成果……………………………………………………. 22
第四章、討論…………………………………………………………. 29
第五章、圖表………………………………………………………… 33
參考文獻…………………………………………………….……….. 51
1.Elvin, J.G.; Couston, R.G.; van der Walle, C.F., Therapeutic antibodies: market considerations, disease targets and bioprocessing. International Journal of Pharmaceutics, 2013. 440(1):83-98.
2.Pavlou, A.K.; Belsey, M.J., The therapeutic antibodies market to 2008. European Journal of Pharmaceutics and Biopharmaceutics, 2005. 59(3):389-96.
3.Andrew, M.S.; James P.A.; Jedd D.W., Monoclonal antibodies in cancer therapy. Cancer Immunity, 2012. 12(14)
4.Xu, H.; Yu, Y.; Marciniak, D.; Rishi, A.K.; Sarkar, F.H.; Kucuk, O.; Majumdar, A.P.., Epidermal growth factor receptor (EGFR)-related protein inhibits multiple members of the EGFR family in colon and breast cancer cells. Molecular Cancer Therapeutics, 2005. 4(3):435-42.
5.Moulder, S.L.; Yakes, F.M.; Muthuswamy, S.K.; Bianco, R.; Simpson, J.F.; Arteaga, C.L., Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Research, 2001. 61(24):8887-95.
6.Baselga, J., The EGFR as a target for anticancer therapy--focus on cetuximab. European Journal of Cancer, 2001. 37 (l 4):16-22.
7.Dunn, E.F.; Iida, M.; Myers, R.A.; Campbell, D.A.; Hintz, K.A.; Armstrong, E.A.; Li, C.; Wheeler, D.L., Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab. Oncogene, 2011. 30(5):561-74.
8.Xiang, J.; Chen, Z., Genetic engineering of high affinity anti-human colorectal tumour mouse/human chimeric antibody. Immunology, 1992. 75(2): 209–216.
9.Verhoeyen, M.; Milstein, C.; Winter, G., Reshaping human antibodies: grafting an antilysozyme activity. Science, 1988. 239(4847):1534-6.
10.Riechmann, L.; Clark, M.; Waldmann, H.; Winter, G., Reshaping human antibodies for therapy. Nature, 1988. 332(6162):323-7.
11.Jones, P.T.; Dear, P.H.; Foote, J.; Neuberger, M.S.; Winter, G., Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature, 1986. 321(6069):522-5.
12.Allen, D.; Simon, T.; Sablitzky, F.; Rajewsky, K.; Cumano, A., Antibody engineering for the analysis of affinity maturation of an anti-hapten response. The EMBO Journal, 1988. 7(7):1995-2001.
13.Roberts, S.; Cheetham, J.C.; Rees, A.R., Generation of an antibody with enhanced affinity and specificity for its antigen by protein engineering. Nature, 1987. 328(6132):731-4.
14.Rudikoff, S.; Giusti, A.M.; Cook, W.D.; Scharff, M.D., Single amino acid substitution altering antigen binding specificity. Proceedings of the National Academy of Sciences of the United States of America, 1982. 79(6):1979-83.
15.Lippow, S.M.; Wittrup, K.D.; Tidor, B., Computational design of antibody-affinity improvement beyond in vivo maturation. Nature Biotechnology, 2007. 25(10):1171-6.
16.Wong, S.F., Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Clinical Therapeutics, 2005. 27(6):684-94.
17.Vogel, C.L.; Cobleigh, M.A.; Tripathy, D.; Gutheil, J.C.; Harris, L.N.; Fehrenbacher, L.; Slamon, D.J.; Murphy, M.; Novotny, W.F.; Burchmore, M.; Shak, S.; Stewart, S.J.; Press, M., Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. Journal of Clinical Oncology, 2002. 20(3):719-26.
18.Proba, K.; Honegger, A.; Plückthun, A., Natural antibody missing a cysteine in VH: consequences for thermodynamic stability and folding. The Journal of Molecular Biology. 1997. 265(2):161-72.
19.Welschof, M.; Terness, P.; Kolbinger, F.; Zewe, M.; Dübel, S.; Dörsam, H.; Hain, C.; Finger, M.; Jung, M.; Moldenhauer, G., Amino acid sequence based PCR primers for amplification of rearranged human heavy and light chain immunoglobulin variable region genes. Journal of Immunological Methods, 1995. 179(2):203-14.
20.Turk, B.E.; Huang, L.L.; Piro, E.T.; Cantley, L.C., Determination of protease cleavage site motifs using mixture-based oriented peptide libraries. Nature Biotechnology, 2001. 19(7):661-7.
21.Chen, Y.; Wiesmann, C.; Fuh, G.; Li, B.; Christinger, H.W.; McKay, P.; de Vos, A.M.; Lowman, H.B., Election and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen. The Journal of Molecular Biology, 1999. 293(4):865-81
22.Kryczka, J.; Stasiak, M.; Dziki, L.; Mik, M.; Dziki, A.; Cierniewski, C., Matrix metalloproteinase-2 cleavage of the β1 integrin ectodomain facilitates colon cancer cell motility. The Journal of Biological Chemistry, 2012. 287(43):36556-66.
23.Jiao, Y.; Feng, X.; Zhan, Y.; Wang, R.; Zheng, S.; Liu, W.; Zeng, X., Matrix metalloproteinase-2 promotes αvβ3 integrin-mediated adhesion and migration of human melanoma cells by cleaving fibronectin. PLoS One. 2012. 7(7):e41591.
24.Roomi, M.W.; Monterrey, J.C.; Kalinovsky, T.; Rath, M.; Niedzwiecki, A., Patterns of MMP-2 and MMP-9 expression in human cancer cell lines. Oncology Reports. 2009. 21(5):1323-33.
25.Brun, J.L.; Cortez, A.; Commo, F.; Uzan, S.; Rouzier, R.; Daraï, E., Serous and mucinous ovarian tumors express different profiles of MMP-2, -7, -9, MT1-MMP, and TIMP-1 and -2. International Journal of Oncology. 2008. 33(6):1239-46.
26.Orimoto, A.M.; Neto, C.F.; Pimentel, E.R.; Sanches, J.A.; Sotto, M.N.; Akaishi, E.; Ruiz, I.R., High numbers of human skin cancers express MMP2 and several integrin genes. Journal of Cutaneous Pathology. 2008. 35(3):285-91.
27.Yang, X.D.; Jia, X.C.; Corvalan, J.R.; Wang, P.; Davis, C.G., Development of ABX-EGF,a fully human anti-EGF receptor monoclonal antibody for cancer therapy. Critical Reviews in Oncology /Hematology. 2001. 38(1):17-23.
28.Makabe, K.; Nakanishi, T.; Tsumoto, K.; Tanaka, Y.; Kondo, H.; Umetsu, M.; Sone, Y.; Asano, R.; Kumagai, I., Thermodynamic consequences of mutations in vernier zone residues of a humanized anti-human epidermal growth factor receptor murine antibody, 528. The Journal of Biological Chemistry. 2008. 283(2):1156-66.
29.Cunningham, D.; Humblet, Y.; Siena, S.; Khayat, D.; Bleiberg, H.; Santoro, A.; Bets, D.; Mueser, M.; Harstrick, A.; Verslype, C.; Chau, I.; Van, Cutsem, E., Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. The New England Journal of Medicine. 2004. 351(4):337-45
30.Watanabe, N.; Otsuka, S.; Sasaki, Y.; Shimojima, R.; Wani, Y.; Uchino, K.; Cardiac tolerability of concurrent administration of trastuzumab and anthracycline-based regimen as adjuvant chemotherapy for breast cancer. Breast Care. 2014. 9(1):46-51.
31.Baldassano, R.; Braegger, C.P.; Escher, J.C.; DeWoody, K.; Hendricks, D.F.; Keenan, G.F.; Winter, H.S., Infliximab (REMICADE) therapy in the treatment of pediatric Crohn''s disease. The American Journal of Gastroenterology. 2003. 98(4):833-8.
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