化工学报 ›› 2018, Vol. 69 ›› Issue (1): 341-351.DOI: 10.11949/j.issn.0438-1157.20171040
卢慧丽, 林东强, 姚善泾
收稿日期:
2017-08-01
修回日期:
2017-10-26
出版日期:
2018-01-05
发布日期:
2018-01-05
通讯作者:
姚善泾
基金资助:
国家自然科学基金项目(21576233,21476198);中国博士后科学基金项目(512100-X91603)。
LU Huili, LIN Dongqiang, YAO Shanjing
Received:
2017-08-01
Revised:
2017-10-26
Online:
2018-01-05
Published:
2018-01-05
Contact:
10.11949/j.issn.0438-1157.20171040
Supported by:
supported by the National Natural Science Foundation of China(21576233, 21476198).
摘要:
抗体,特别是单克隆抗体是一类重要的生物技术药物,具有巨大的市场前景。目前抗体药物生产的瓶颈已由抗体表达转移到抗体的分离纯化中,其中层析是最关键的技术。典型的抗体纯化过程首先通过蛋白A亲和层析对抗体进行捕获,然后进一步精制,主要方法包括离子交换层析、疏水相互作用层析以及羟基磷灰石层析等,这些传统的层析方法不可避免存在一定的局限性。为此,研究者致力于开发合适的新方法,如疏水性电荷诱导层析和短肽仿生层析等,很好地弥补了传统层析方法的不足。本文根据近年来国内外在单抗药物分离纯化方面所取得的研究进展,着重介绍了在单抗分离纯化中的常用的层析技术及研究进展。
中图分类号:
卢慧丽, 林东强, 姚善泾. 抗体药物分离纯化中的层析技术及进展[J]. 化工学报, 2018, 69(1): 341-351.
LU Huili, LIN Dongqiang, YAO Shanjing. Chromatographic technology in antibody purification and its progress[J]. CIESC Journal, 2018, 69(1): 341-351.
[1] | AYYAR B V, ARORA S, O'KENNEDY R. Coming-of-age of antibodies in cancer therapeutics[J]. Trends in Pharmacological Sciences, 2016, 37(12):1009-1028. |
[2] | LI F, VIJAYASANKARAN N, SHEN A Y, et al. Cell culture processes for monoclonal antibody production[J]. Mabs, 2010, 2(5):466-477. |
[3] | ROQUE A C, LOWE C R, TAIPA M Â. Antibodies and genetically engineered related molecules:production and purification[J]. Biotechnology Progress, 2004, 20(3):639-654. |
[4] | SHUKLA A A, THÖMMES J. Recent advances in large-scale production of monoclonal antibodies and related proteins[J]. Trends in Biotechnology, 2010, 28(5):253-261. |
[5] | BIRCH J R, RACHER A J. Antibody production[J]. Advanced Drug Delivery Reviews, 2006, 58(5/6):671-685. |
[6] | HOBER S, NORD K, LINHULT M. Protein a chromatography for antibody purification[J]. Journal of Chromatography B Analytical Technologies in the Biomedical & Life Sciences, 2007, 848(1):40-47. |
[7] | FAHRNER R L, KNUDSEN H L, BASEY C D, et al. Industrial purification of pharmaceutical antibodies:development, operation, and validation of chromatography processes[J]. Biotechnology & Genetic Engineering Reviews, 2001, 18(1):301-328. |
[8] | BLOOM J W, WONG M F, MITRA G. Detection and reduction of protein a contamination in immobilized protein a purified monoclonal antibody preparations[J]. Journal of Immunological Methods, 1989, 117(1):83-89. |
[9] | F Ü GLISTALLER P. Comparison of immunoglobulin binding capacities and ligand leakage using eight different protein a affinity chromatography matrices[J]. 1989, 124(2):171-177. |
[10] | LINHULT M, GU LICH S, GRA SLUND T, et al. Improving the tolerance of a protein a analogue to repeated alkaline exposures using a bypass mutagenesis approach[J]. Proteins Structure Function & Bioinformatics, 2004, 55(2):407-416. |
[11] | PABST T M, PALMGREN R, FORSS A, et al. Engineering of novel staphylococcal protein a ligands to enable milder elution pH and high dynamic binding capacity[J]. Journal of Chromatography A, 2014, 1362:180-185. |
[12] | WATANABE H, MATSUMARU H, OOISHI A, et al. Structure-based histidine substitution for optimizing pH-sensitive staphylococcus protein A[J]. Journal of Chromatography B Analytical Technologies in the Biomedical & Life Sciences, 2013, 929(929C):155. |
[13] | TSUKAMOTO M, WATANABE H, OOISHI A, et al. Engineered protein a ligands, derived from a histidine-scanning library, facilitate the affinity purification of IgG under mild acidic conditions[J]. Journal of Biological Engineering, 2014, 8(1):1-9. |
[14] | 王荣柱. 以四肽为配基的仿生层析和抗体的分离纯化[D]. 杭州:浙江大学, 2015:14-18. WANG R Z. Research on tetrapeptide biomimetic chromatography for antibody purification[D]. Hangzhou:Zhejiang University, 2015:14-18. |
[15] | BOLTON G R, MEHTA K K. The role of more than 40 years of improvement in protein a chromatography in the growth of the therapeutic antibody industry[J]. Biotechnology Progress, 2016, 32(5):1193-1202. |
[16] | CHON J H, ZARBIS-PAPASTOITSIS G. Advances in the production and downstream processing of antibodies[J]. New Biotechnology, 2011, 28(5):458-463. |
[17] | 童红飞. 新型疏水性电荷诱导配基设计及层析分离抗体研究[D]. 杭州:浙江大学, 2014:18-22. TONG H F. Antibody separation by hydrophobic charge-induction chromatography and novel ligand design[D]. Hangzhou:Zhejiang University, 2014:18-22. |
[18] | SVASTI J, MILSTEIN C. The disulphide bridges of a mouse immunoglobulin G1 protein[J]. Biochemical Journal, 1972, 126(4):837-850. |
[19] | JUNGBAUER A. Chromatographic media for bioseparation[J]. J. Chromatogr. A, 2005, 1065(1):3-12. |
[20] | LOW D, O'LEARY R, PUJAR N S. Future of antibody purification[J]. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 848(1):48-63. |
[21] | FOLLMAN D K, FAHRNER R L. Factorial screening of antibody purification processes using three chromatography steps without protein A[J]. Journal of Chromatography A, 2004, 1024(1):79-85. |
[22] | JIANG C, FLANSBURG L, GHOSE S, et al. Defining process design space for a hydrophobic interaction chromatography(HIC) purification step:application of quality by design(QBD) principles[J]. Biotechnology & Bioengineering, 2010, 107(6):985-997. |
[23] | LU Y, WILLIAMSON B, GILLESPIE R. Recent advancement in application of hydrophobic interaction chromatography for aggregate removal in industrial purification process[J]. Current Pharmaceutical Biotechnology, 2009, 10(4):427-433. |
[24] | GHOSE S, TAO Y, CONLEY L, et al. Purification of monoclonal antibodies by hydrophobic interaction chromatography under no-salt conditions[J]. Mabs, 2013, 5(5):795-800. |
[25] | TISELIUS A, HJERTEN S, LEVIN O. Protein chromatography on calcium phosphate columns[J]. Archives of Biochemistry & Biophysics, 1956, 65(1):132-155. |
[26] | GORBUNOFF M J. The interaction of proteins with hydroxyapatite(I):Role of protein charge and structure[J]. Analytical Biochemistry, 1984, 136(2):425-432. |
[27] | GORBUNOFF M J. The interaction of proteins with hydroxyapatite(Ⅱ):Role of acidic and basic groups[J]. Analytical Biochemistry, 1984, 136(2):433-439. |
[28] | GORBUNOFF M J, TIMASHEFF S N. The interaction of proteins with hydroxyapatite(Ⅲ):Mechanism[J]. Analytical Biochemistry, 1984, 136(2):440-445. |
[29] | GAGNON P, NG P, ZHEN J, et al. A ceramic hydroxyapatite based purification platform[J]. BioProcess International, 2006, (2):50-60. |
[30] | BURTON S C, HARDING D R. Salt-independent adsorption chromatography:new broad-spectrum affinity methods for protein capture[J]. Journal of Biochemical and Biophysical Methods, 2001, 49(1):275-287. |
[31] | HAMILTON G E, LUECHAU F, BURTON S C, et al. Development of a mixed mode adsorption process for the direct product sequestration of an extracellular protease from microbial batch cultures[J]. Jounal of Biotechnology, 2000, 79(2):103-115. |
[32] | GUERRIER L, FLAYEUX I, BOSCHETTI E. A dual-mode approach to the selective separation of antibodies and their fragments[J]. Journal of Chromatography B:Biomedical Sciences and Applications, 2001, 755(1):37-46. |
[33] | YAN J, ZHANG Q L, LIN D Q, et al. Protein adsorption behavior and immunoglobulin separation with a mixed-mode resin based on p-aminohippuric acid[J]. Journal of Separation Science, 2014, 37(18):2474-2480. |
[34] | TONG H F, LIN D Q, ZHANG Q L, et al. Molecular recognition of Fc-specific ligands binding onto the consensus binding site of IgG:insights from molecular simulation[J]. Journal of Molecular Recognition, 2014, 27(8):501-509. |
[35] | GUERRIER L, GIROT P, SCHWARTZ W, et al. New method for the selective capture of antibodies under physiolgical conditions[J]. Bioseparation, 2000, 9(4):211-221. |
[36] | TONG H F, LIN D Q, YUAN X M, et al. Enhancing IgG purification from serum albumin containing feedstock with hydrophobic charge-induction chromatography[J]. Journal of Chromatography A, 2012, 1244:116-122. |
[37] | TONG H F, LIN D Q, GAO D, et al. Caprylate as the albumin-selective modifier to improve IgG purification with hydrophobic charge-induction chromatography[J]. Journal of Chromatography A, 2013, 1285:88-96. |
[38] | ARAKAWA T, KITA Y, SATO H, et al. MEP chromatography of antibody and Fc-fusion protein using aqueous arginine solution[J]. Protein Expression & Purification, 2008, 63(2):158-163. |
[39] | BURTON S C, HARDING D R K. Hydrophobic charge induction chromatography:salt independent protein adsorption and facile elution with aqueous buffers[J]. Journal of Chromatography A, 1998, 814(1/2):71-81. |
[40] | XIA H F, LIN D Q, WANG L P, et al. Preparation and evaluation of cellulose adsorbents for hydrophobic charge induction chromatography[J]. Industrial & Engineering Chemistry Research, 2008, 47(23):9566-9572. |
[41] | LU H L, LIN D Q, GAO D, et al. Evaluation of immunoglobulin adsorption on the hydrophobic charge-induction resins with different ligand densities and pore sizes[J]. Journal of Chromatography A, 2013, 1278:61-68. |
[42] | LU H L, LIN D Q, ZHANG Q L, et al. Evaluation on adsorption selectivity of immunoglobulin G with 2-mercapto-1-methyl-imidazole-based hydrophobic charge-induction resins[J]. Biochemical Engineering Journal, 2017, 119:34-41 |
[43] | SHI W, LIN D Q, TONG H F, et al. 5-aminobenzimidazole as new hydrophobic charge-induction ligand for expanded bed adsorption of bovine IgG[J]. Journal of Chromatography A, 2015, 1425:97-105. |
[44] | YAN J, ZHANG Q L, TONG H F, et al. Hydrophobic charge-induction resin with 5-aminobenzimidazol as the functional ligand:preparation, protein adsorption and immunoglobulin G purification[J]. Journal of Separation Science, 2015, 38:2387-2393. |
[45] | GU J L, TONG H F, LIN D Q. Evaluation of magnetic particles modified with a hydrophobic charge-induction ligand for antibody capture[J]. Journal of Chromatography A, 2016, 1460:61-67. |
[46] | TONG H F, LIN D Q, CHU W N, et al. Multimodal charge-induction chromatography for antibody purification[J]. Journal of Chromatography A, 2015, 1429:258-264. |
[47] | LUO Y D, ZHANG Q L, YUAN X M, et al. Selectivity evaluation and separation of human immunoglobulin G, Fab and Fc fragments with mixed-mode resins[J]. Journal of Chromatography B Analytical Technologies in the Biomedical & Life Sciences, 2016, 1040:105-110. |
[48] | O'CONNOR E, ASPELUND M, BARTNIK F, et al. Monoclonal antibody fragment removal mediated by mixed mode resins[J]. Journal of Chromatography A, 2017, 1499:65-77 |
[49] | GAO D, WANG L L, LIN D Q, et al. Evaluating antibody monomer separation from associated aggregates using mixed-mode chromatography[J]. Journal of Chromatography A, 2013, 1294(11):70-75. |
[50] | CHEN J, TETRAULT J, ZHANG Y, et al. The distinctive separation attributes of mixed-mode resins and their application in monoclonal antibody downstream purification process[J]. Journal of Chromatography A, 2010, 1217(2):216-224. |
[51] | ARAKAWA T, KUROSAWA Y, STORMS M, et al. Capto MMC mixed-mode chromatography of murine and rabbit antibodies[J]. Protein Expression & Purification, 2016, 127:105-110. |
[52] | MARIA S, JOUCLA G, GARBAY B, et al. Purification process of recombinant monoclonal antibodies with mixed mode chromatography[J]. Journal of Chromatography A, 2015, 1393:57-64. |
[53] | WOLFE L S, BARRINGER C P, MOSTAFA S S, et al. Multimodal chromatography:characterization of protein binding and selectivity enhancement through mobile phase modulators[J]. Journal of Chromatography A, 2014, 1340(8):151-156. |
[54] | SCHWARTZ W, JUDD D, WYSOCKI M, et al. Comparison of hydrophobic charge induction chromatography with affinity chromatography on protein A for harvest and purification of antibodies[J]. Journal of Chromatography A, 2001, 908(1/2):251-263. |
[55] | CHEN J, TETRAULT J, LEY A. Comparison of standard and new generation hydrophobic interaction chromatography resins in the monoclonal antibody purification process[J]. J. Chromatogr A, 2008, 1177(2):272-281. |
[56] | GHOSE S, HUBBARD B, CRAMER S M. Evaluation and comparison of alternatives to protein a chromatography-mimetic and hydrophobic charge induction chromatographic stationary phases[J]. Journal of Chromatography A, 2006, 1122(1/2):144-152. |
[57] | SHUKLA A A, HUBBARD B, TRESSEL T, et al. Downstream processing of monoclonal antibodies-application of platform approaches[J]. Journal of Chromatography B, 2007, 848(1):28-39. |
[58] | YANG H, GURGEL P V, CARBONELL R G. Purification of human immunoglobulin G via Fc-specific small peptide ligand affinity chromatography[J]. Journal of Chromatography A, 2009, 1216(6):910-918. |
[59] | YANG H, GURGEL P V, WILLIAMS D K, et al. Binding site on human immunoglobulin G for the affinity ligand HWRGWV[J]. Journal of Molecular Recognition, 2010, 23(3):271-282. |
[60] | NAIK A D, MENEGATTI S, GURGEL P V, et al. Performance of hexamer peptide ligands for affinity purification of immunoglobulin G from commercial cell culture media[J]. Journal of Chromatography A, 2011, 1218(13):1691-1700. |
[61] | MENEGATTI S, NAIK A D, GURGEL P V, et al. Alkaline-stable peptide ligand affinity adsorbents for the purification of biomolecules[J]. Journal of Chromatography A, 2012, 1245(13):55-64. |
[62] | GEYSEN H M, RODDA S J, MASON T J. A priori delineation of a peptide which mimics a discontinuous antigenic determinant[J]. Molecular Immunology, 1986, 23(7):709-715. |
[63] | 任军, 贾凌云. 亲和色谱仿生配基的筛选和设计[J]. 分析化学, 2005, 33(9):1345-1349. REN J, JIA L Y. Screening and design of affinity chromatography biomimetic ligand[J]. Chinese Journal of Analytical Chemistry, 2005, 33(9):1345-1349. |
[64] | FASSINA G, VERDOLIVA A, ODIERNA M R, et al. Protein a mimetic peptide ligand for affinity purification of antibodies[J]. Journal of Molecular Recognition, 1996, 9(5/6):564-569. |
[65] | FASSINA G, VERDOLIVA A, PALOMBO G, et al. Immunoglobulin specificity of TG19318:a novel synthetic ligand for antibody affinity purification[J]. Journal of Molecular Recognition, 1998, 11(1-6):128-133. |
[66] | PALOMBO G, FALCO S D, TORTORA M, et al. A synthetic ligand for IgA affinity purification[J]. Journal of Molecular Recognition, 1998, 11(1-6):243-246. |
[67] | PALOMBO G, ROSSI M, CASSANI G, et al. Affinity purification of mouse monoclonal ige using a protein a mimetic ligand(TG19318) immobilized on solid supports[J]. Journal of Molecular Recognition, 1998, 11(1-6):247-249. |
[68] | PALOMBO G, VERDOLIVA A, FASSINA G. Affinity purification of immunoglobulin m using a novel synthetic ligand[J]. Journal of Chromatography B Biomedical Sciences & Applications, 1998, 715(1):137-145. |
[69] | VERDOLIVA A, PANNONE F, ROSSI M, et al. Affinity purification of polyclonal antibodies using a new all-D synthetic peptide ligand:comparison with protein A and protein G[J]. Journal of Immunological Methods, 2002, 271(271):77-88. |
[70] | YANG H, GURGEL P V, CARBONELL R G. Hexamer peptide affinity resins that bind the Fc region of human immunoglobulin G[J]. Journal of Peptide Research, 2005, 66(s1):120-137. |
[71] | NAIK A D, MENEGATTI S, REESE H R, et al. Process for purification of monoclonal antibody expressed in transgenic lemna plant extract using dextran-coated charcoal and hexamer peptide affinity resin[J]. Journal of Chromatography A, 2012, 1260(20):61-66. |
[72] | BILLAKANTI J M, FEE C J, NAIK A D, et al. Application of peptide chromatography for the isolation of antibodies from bovine skim milk, acid whey and colostrum[J]. Food & Bioproducts Processing, 2014, 92(2):199-207. |
[73] | LIU Z, GURGEL P V, CARBONELL R G. Affinity chromatographic purification of human immunoglobulin M from human B lymphocyte cell culture supernatant[J]. Biochemical Engineering Journal, 2013, 70(2):63-70. |
[74] | ZHAO W W, LIU F F, SHI Q H, et al. Biomimetic design of affinity peptide ligands for human IgG based on protein A-IgG complex[J]. Biochemical Engineering Journal, 2014, 88(28):1-11. |
[75] | ZHAO W W, LIU F F, SHI Q H, et al. Octapeptide-based affinity chromatography of human immunoglobulin G:comparisons of three different ligands[J]. Journal of Chromatography A, 2014, 1359:100-111. |
[76] | ZHAO W W, SHI Q H, YAN S. FYWHCLDE-based affinity chromatography of IgG:effect of ligand density and purifications of human IgG and monoclonal antibody[J]. Journal of Chromatography A, 2014, 1355:107-114. |
[77] | WANG R Z, LIN D Q, CHU W N, et al. New tetrapeptide ligands designed for antibody purification with biomimetic chromatography:molecular simulation and experimental validation[J]. Biochemical Engineering Journal, 2016, 114:191-201. |
[78] | STEFANO M, MAHMUD H, AMITH D N, et al. Mrna display selection and solid-phase synthesis of Fc-binding cyclic peptide affinity ligands[J]. Biotechnology & Bioengineering, 2013, 110(3):857-870. |
[79] | KANG H J, CHOE W, MIN J K, et al. Cyclic peptide ligand with high binding capacity for affinity purification of immunoglobulin G[J]. Journal of Chromatography A, 2016, 1466:105-112. |
[1] | 赵亚欣, 张雪芹, 王荣柱, 孙国, 姚善泾, 林东强. 流穿模式离子交换层析去除单抗聚集体[J]. 化工学报, 2023, 74(9): 3879-3887. |
[2] | 宋明昊, 赵霏, 刘淑晴, 李国选, 杨声, 雷志刚. 离子液体脱除模拟油中挥发酚的多尺度模拟与研究[J]. 化工学报, 2023, 74(9): 3654-3664. |
[3] | 胡建波, 刘洪超, 胡齐, 黄美英, 宋先雨, 赵双良. 有机笼跨细胞膜易位行为的分子动力学模拟研究[J]. 化工学报, 2023, 74(9): 3756-3765. |
[4] | 赵佳佳, 田世祥, 李鹏, 谢洪高. SiO2-H2O纳米流体强化煤尘润湿性的微观机理研究[J]. 化工学报, 2023, 74(9): 3931-3945. |
[5] | 汪林正, 陆俞冰, 张睿智, 罗永浩. 基于分子动力学模拟的VOCs热氧化特性分析[J]. 化工学报, 2023, 74(8): 3242-3255. |
[6] | 陈吉, 洪泽, 雷昭, 凌强, 赵志刚, 彭陈辉, 崔平. 基于分子动力学的焦炭溶损反应及其机理研究[J]. 化工学报, 2023, 74(7): 2935-2946. |
[7] | 董明, 徐进良, 刘广林. 超临界水非均质特性分子动力学研究[J]. 化工学报, 2023, 74(7): 2836-2847. |
[8] | 刘远超, 蒋旭浩, 邵钶, 徐一帆, 钟建斌, 李耑. 几何尺寸及缺陷对石墨炔纳米带热输运特性的影响[J]. 化工学报, 2023, 74(6): 2708-2716. |
[9] | 顾浩, 张福建, 刘珍, 周文轩, 张鹏, 张忠强. 力电耦合作用下多孔石墨烯膜时间维度的脱盐性能及机理研究[J]. 化工学报, 2023, 74(5): 2067-2074. |
[10] | 李辰鑫, 潘艳秋, 何流, 牛亚宾, 俞路. 基于碳微晶结构的炭膜模型及其气体分离模拟[J]. 化工学报, 2023, 74(5): 2057-2066. |
[11] | 廖艺, 牛亚宾, 潘艳秋, 俞路. 复配表面活性剂对油水界面行为和性质影响的模拟研究[J]. 化工学报, 2022, 73(9): 4003-4014. |
[12] | 杨松涛, 李东洋, 牛玉清, 李鑫钢, 康绍辉, 李洪, 叶开凯, 周志全, 高鑫. 氟化物势能函数和热力学性质的分子模拟研究进展[J]. 化工学报, 2022, 73(9): 3828-3840. |
[13] | 郑默, 李晓霞. ReaxFF MD模拟揭示的煤热解挥发分自由基反应的竞争与协调[J]. 化工学报, 2022, 73(6): 2732-2741. |
[14] | 王江丽, 薛敏, 赵承科, 岳凤霞. 木质素分级对其应用性能的影响[J]. 化工学报, 2022, 73(5): 1894-1907. |
[15] | 李春晖, 何辉, 何明键, 张萌, 高杨, 矫彩山. 离子液体萃取硝酸中Ce(Ⅳ)的动力学研究[J]. 化工学报, 2022, 73(4): 1606-1614. |
阅读次数 | ||||||||||||||||||||||||||||||||||||||||||||||||||
全文 1792
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||
摘要 879
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||