肝癌导向治疗中新型导向肽的筛选及初步应用研究
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摘要
原发性肝癌是一种分布范围较广、危害严重的致死性疾病。我国一直以来都是肝癌高发地区,每年至少有12万人死于原发性肝癌,因此建立起一套有效的肝癌临床检测和治疗体系也就成为了一项关系到人民生命健康的重要工程。
     目前肝癌靶向治疗领域普遍采用的依然是单抗及其片段作为治疗药物的特异性载体,由于单克隆抗体特异性的识别能力和所特有的免疫学功能,在整个肿瘤靶向治疗领域已经取得了极大的成功,甚至某些单克隆抗体已经通过美国FDA的认证正式走向临床应用。尽管如此,单克隆抗体技术的应用依然存在一些难以逾越的障碍:分子量大以及异源性所诱导机体产生不良的免疫反应,由此对患者的身体造成伤害,同时还会大大降低靶向药物的生物半衰期,进而影响到整个的肿瘤治疗效果。
     本论文拟利用体内噬菌体展示肽库技术,筛选到在体内具有特异性结合能力的肝癌肿瘤组织特异性粘附肽,进而利用这些特异性高、结合能力强的肝癌特异性粘附肽来取代传统靶向治疗治疗领域中单克隆抗体的作用,充分利用多肽靶向载体的分子量低、免疫原性小的特点,弥补单克隆抗体的不足,建立一套切实有效的基于多肽的肝癌鉴定和靶向治疗系统。
     本论文主要分成以下几个部分:
     一、 体内噬菌体肽库技术筛选肝癌组织特异性粘附肽
     1.利用广泛采用的NEB公司的噬菌体线性12肽文库,在本实验室构建的荷肝癌细胞Bel-7402细胞株的荷瘤裸鼠体内,通过三轮的体内筛选,得到大量在体内具有特异性靶向能力的噬菌体克隆。
     2.在每轮筛选的过程中,利用噬菌体效价的测定及时监测和比较裸鼠体内各个组织中噬菌体的数目;同时采用免疫组织化学的方法,对组织中噬菌体的分布情况进行观察。结合噬菌体数目的定量分析和免疫组织化学的定性分析,可以看出:通过三轮的体内筛选,特异性结合的噬菌体在肿瘤组织中得到了有效的富集。
     3.在对筛选得到的噬菌体进行单克隆化后,随机选取了46个噬菌体克隆进行测序,并对所得到的DNA序列进行比对和分析。通过分析,我们将得到的噬菌体根据所含相同序列的特点初步分为PSS/PTT、PPS、RW以及PRA组,并依次确定了每组中最具代表性的多个候选阳性克隆。
Human hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. China is one of the most widespread countries of HCC. At least 120,000 people in China were dead from it every year. So it is very important to establish a convenient and reliable system in clinical diagnosis and treatments of hepatocarcinoma.
    Now the monoclonal antibody and its fragment is still the common used carrier in hepatocarcinoma targeting therapy. Because of the specifically discernment and immunity functional the MAb has become most succeed one in the tumor targeting therapy field. Even some MAb have got the authentication of FDA in USA, the MAb still has its inborn shortcomings: higher molecular weight and immunogenic could induce some bad responses to human body, and these responses will hurt to patients obviously. Then the shortcomings could also decrease the half life of immunotoxin and the therapy effect will also been reduced eventually.
    In this paper, we will try to screen some specifically binding peptides to hepatocarcinoma tissues by using in vivo phage display technology. Then we can use this peptides which have high specifically and strong binding ability to take the place of monoclonal antibody in traditional tumor targeting therapy. Making the most use of specifically binding peptides' lower molecular weight and immunogenic to make up the shortcomings of MAb and to establish a feasible peptides system for diagnosis and targeting therapy to hepatocarcinoma.
    This paper can be divided into three parts:
    A. The panning of specifically binding peptides to hepatocarcinoma by in vivo phage display technology.
    a) The common used Ph.D.-12 Phage Display Peptide Library Kit which produced by New England Biolabs Inc was chosen to injected into the nude mouse with hepatocarcinoma tumors on their backs, after three rounds panning a lot of candidate specifically binding phages were obtained.
    b) Accompanying with each round panning, the phages' titering was carried out as the kit manual to inspect the number of phages in each tissues, and the immunohistochemistry assay was also performed to appraise the distribution of phages in each tissue. From the data of titering and immunohistochemistry we can say that after the three rounds panning the specifically binding phages were enriched effectively to the tumor tissue.
    c) Then the specifically binding clones were picked out for random amplification. There are 46 clones were chosen for sequencing eventually and the sequence of those phage clones were compared and analyzed. From the sequence we can say that also the data are all complex we still
引文
1. Parkin, D. M., Pisani, P., and Ferlay, J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int. J. Cancer, 80: 827-841, 1999.
    2. Pisani, P., Parkin, D. M., Bray, F., and Ferlay, J. Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer, 83: 18-29, 1999.
    3. Gerard, B. and Bleiberg, H. Treatment of hepatocarcinoma. Curr. Oncol. Rep., 6: 184-191, 2004.
    4. Immunological Approaches to Tumor Therapy. Proceedings from the Ⅲ International Meeting on ldiotypic Network and Tumor Therapy by Gene Therapy, Drug Targeting, Vaccination, and Photodynamic Therapy. Bonn, Germany, February 29-March 2, 1996. Hybridoma, 16: 1-137, 1997.
    5. Xia, J., Ren, Z., Ye, S., Sharma, D., Lin, Z., Gan,Y., Chen, Y., Ge, N., Ma, Z., Wu, Z., Fan, J., Qin, L., Zhou, X., Tang, Z., and Yang, B. Study of severe and rare complications oftransarterial chemoembolization (TACE) for liver cancer. Eur. J. Radiol., 2006.
    6. Hildebrand, P., Kleemann, M., Roblick, U. J., Mirow, L., Birth, M., Leibecke, T., and Bruch, H. P. Radiofrequency-ablation of unresectable primary and secondary liver tumors: results in 88 patients. Langenbecks Arch. Surg., 391: 1-6, 2006.
    7. Jurcic, J. G. Immunotherapy for acute myeloid leukemia. Curr. Oncol. Rep., 7: 339-346, 2005.
    8. Ledley, F. D. Nonviral gene therapy: the promise of genes as pharmaceutical products. Hum. Gene Ther., 6: 1129-1144, 1995.
    9. Koga, S. and Kanetake, H. [Progress in therapeutic strategy for renal cell carcinoma]. Gan To Kagaku Ryoho, 33: 171-177, 2006.
    10. Qian, C., Drozdzik, M., Caselmann, W. H., and Prieto, J. The potential ofgene therapy in the treatment of hepatocellular carcinoma. J. Hepatol., 32: 344-351, 2000.
    11. Waldmann, T. A. Immunotherapy: past, present and future. Nat. Med., 9: 269-277, 2003.
    12. Atarashi, Y., Yasumura, S., Nambu, S., Yoshio, Y., Murakami, J., Takahara, T., Higuchi, K., Watanabe, A., Miyata, K., and Kato, M. A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: implication for immunotherapy of human hepatocellular carcinoma. Hepatology, 28: 57-67, 1998.
    13. Kubo, S., Nishiguchi, S., Hirohashi, K., Tanaka, H., Shuto, T., and Kinoshita, H. Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy. Br. J. Surg., 89: 418-422, 2002.
    14. Lin, S. M., Lin, C. J., Hsu, C. W., Tai, D. I., Sheen, I. S., Lin, D. Y., and Liaw, Y. F. Prospective randomized controlled study of interferon-alpha in preventing??hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors. Cancer, 100: 376-382, 2004.
    
    15. Takayama, T., Sekine, T., Makuuchi, M., Yamasaki, S., Kosuge, T., Yamamoto, J., Shimada, K., Sakamoto, M., Hirohashi, S., Ohashi, Y, and Kakizoe, T. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet, 356: 802-807, 2000.
    
    16. O'Beirne, J. P. and Harrison, P. M. The role of the immune system in the control of hepatocellular carcinoma. Eur.J.Gastroenterol.Hepatol., 16: 1257-1260, 2004.
    
    17. Anderson, S. C, Johnson, D. E., Harris, M. P., Engler, H., Hancock, W., Huang, W. M., Wills, K. N., Gregory, R. J., Sutjipto, S., Wen, S. F, Lofgren, S., Shepard, H. M., and Maneval, D. C. p53 gene therapy in a rat model of hepatocellular carcinoma: intra-arterial delivery of a recombinant adenovirus. Clin.Cancer Res., 4: 1649-1659, 1998.
    
    18. Schmitz, V., Qian, C, Ruiz, J., Sangro, B., Melero, I., Mazzolini, G., Narvaiza, I., and Prieto, J. Gene therapy for liver diseases: recent strategies for treatment of viral hepatitis and liver malignancies. Gut, 50: 130-135, 2002.
    
    19. Drozdzik, M., Qian, C, Xie, X., Peng, D., Bilbao, R., Mazzolini, G., and Prieto, J. - Combined gene therapy with suicide gene and interleukin-12 is more efficient than therapy with one gene alone in a murine model of hepatocellular carcinoma. J.Hepatol., 32: 279-286, 2000.
    
    20. Lee, S. O., Lou, W., Qureshi, K. M., Mehraein-Ghomi, F., Trump, D. L., and Gao, A. C. RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells. Prostate, 60: 303-309, 2004.
    
    21. Barajas, M., Mazzolini, G, Genove, G, Bilbao, R., Narvaiza, I., Schmitz, V., Sangro, B., Melero, I., Qian, C, and Prieto, J. Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12. Hepatology, 33: 52-61, 2001.
    
    22. Harada, N., Shimada, M., Okano, S., Suehiro, T, Soejima, Y, Tomita, Y, and Maehara, Y IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice. J.Immunol., 173: 6635-6644, 2004.
    
    23. McCormick, F. Cancer gene therapy: fringe or cutting edge? Nat.Rev.Cancer, 1: 130-141,2001.
    
    24. Jain, R. K. Molecular regulation of vessel maturation. Nat.Med., 9: 685-693,2003.
    
    25. Kinoshita, S., Hirai, R., Yamano, T., Yuasa, I., Tsukuda, K., and Shimizu, N. Angiogenesis inhibitor TNP-470 can suppress hepatocellular carcinoma growth without retarding liver regeneration after partial hepatectomy. Surg.Today, 34: 40-46, 2004.
    
    26. Ikebe, T, Yamamoto, T, Kubo, S., Hirohashi, K., Kinoshita, H., Kaneda, K., and Sakurai, M. Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats. Jpn.J.Cancer Res., 89: 143-149, 1998.
    
    27. Matsumoto, K., Ishikawa, H., Nishimura, D., Hamasaki, K., Nakao, K., and Eguchi, K. Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma. Hepatology, 40: 252-259,2004.
    
    
    28. Ishikawa, H., Nakao, K., Matsumoto, K., Ichikawa, T., Hamasaki, K., Nakata, K., and Eguchi, K. Antiangiogenic gene therapy for hepatocellular carcinoma using angiostatin gene. Hepatology, 37: 696-704, 2003.
    
    29. Schmitz, V., Wang, L., Barajas, M., Gomar, C, Prieto, J., and Qian, C. Treatment of colorectal and hepatocellular carcinomas by adenoviral mediated gene transfer of endostatin and angiostatin-like molecule in mice. Gut, 53: 561-567, 2004.
    
    30. Lin, A. Y., Brophy, N., Fisher, G A., So, S., Biggs, C, Yock, T. I., and Levitt, L. Phase II study of thalidomide in patients with unresectable hepatocellular carcinoma. Cancer, 103: 119-125,2005.
    
    31. Llovet, J. M. and Bruix, J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology, 37: 429-442,2003.
    
    32. Yuen, M. F., Poon, R. T., Lai, C. L, Fan, S. T., Lo, C. M, Wong, K. W., Wong, W. M., and Wong, B. C. A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma. Hepatology, 36: 687-691, 2002.
    
    33. Stern, M. and Herrmann, R. Overview of monoclonal antibodies in cancer therapy: present and promise. Crit Rev.Oncol.Hematol., 54: 11-29, 2005.
    
    34. Kohler, G. and Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. J.Immunol., 174: 2453-2455,2005.
    
    35. Bennett, J. M., Kaminski, M. S., Leonard, J. P., Vose, J. M., Zelenetz, A. D., Knox, S. J., Horning, S., Press, O. W., Radford, J. A., Kroll, S. M., and Capizzi, R. L. Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine 1131 tositumomab. Blood, 105: 4576-4582,2005.
    
    36. Horning, S. J., Younes, A., Jain, V., Kroll, S., Lucas, J., Podoloff, D., and Goris, M. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J.Clin.Oncol., 23: 712-719, 2005.
    
    37. Helguera, G. and Penichet, M. L. Antibody-cytokine fusion proteins for the therapy of cancer. Methods Mol.Med., 109: 347-374, 2005.
    
    38. Penichet, M. L. and Morrison, S. L. Antibody-cytokine fusion proteins for the therapy of cancer. J.Immunol.Methods, 248: 91-101, 2001.
    
    39. McLaughlin, P., Grillo-Lopez, A. J., Link, B. K., Levy, R., Czuczman, M. S., Williams, M. E., Heyman, M. R., Bence-Bruckler, I., White, C. A., Cabanillas, F., Jain, V., Ho, A. D., Lister, J., Wey, K., Shen, D., and Dallaire, B. K. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J.Clin.Oncol., 16: 2825-2833, 1998.
    
    40. Davis, T. A., Grillo-Lopez, A. J., White, C. A., McLaughlin, P., Czuczman, M. S., Link, B. K., Maloney, D. G, Weaver, R. L., Rosenberg, J., and Levy, R. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. J.Clin.Oncol., 18: 3135-3143, 2000.
    
    41. Riechmann, L., Clark, M., Waldmann, H., and Winter, G. Reshaping human antibodies for therapy. Nature, 332: 323-327, 1988.
    
    42. Chen, S. Y. and Marasco, W. A. Novel genetic immunotoxins and intracellular
    antibodies for cancer therapy. Semin.Oncol., 23: 148-153, 1996.
    
    43. Chen, S. Y., Zani, C, Khouri, Y., and Marasco, W. A. Design of a genetic immunotoxin to eliminate toxin immunogenicity. Gene Ther., 2: 116-123, 1995.
    
    44. Pastan, I., Chaudhary, V., and FitzGerald, D. J. Recombinant toxins as novel therapeutic agents. Annu.Rev.Biochem., 61: 331-354, 1992.
    
    45. Panchal, R. G. Novel therapeutic strategies to selectively kill cancer cells. Biochem.Pharmacol., 55: 247-252, 1998.
    
    46. Xu, Y, Xu, Q., Rosenblum, M. G, and Scheinberg, D. A. Antileukemic activity of recombinant humanized M195-gelonin immunotoxin in nude mice. Leukemia, 10: 321-326, 1996.
    
    47. Davol, P., Beitz, J. G, Mohler, M., Ying, W., Cook, J., Lappi, D. A., and Frackelton, A. R., Jr. Saporin toxins directed to basic fibroblast growth factor receptors effectively target human ovarian teratocarcinoma in an animal model. Cancer, 76: 79-85, 1995.
    
    48. Kreitman, R. J., Wilson, W. H., Robbins, D., Margulies, I., Stetler-Stevenson, M., Waldmann, T. A., and Pastan, I. Responses in refractory hairy cell leukemia to a recombinant immunotoxin. Blood, 94: 3340-3348, 1999.
    
    49. Speth, P. A., van Hoesel, Q. G., and Haanen, C. Clinical pharmacokinetics of doxorubicin. Clin.Pharmacokinet., 75: 15-31, 1988.
    
    50. Khayat, D., Antoine, E. C, and Coeffic, D. Taxol in the management of cancers of the breast and the ovary. Cancer Invest, 18: 242-260,2000.
    
    51. Murdter, T. E., Sperker, B., Kivisto, K. T., McClellan, M., Fritz, P., Friedel, G, Linder, A., Bosslet, K., Toomes, H., Dierkesmann, R., and Kroemer, H. K. Enhanced uptake of doxorubicin into bronchial carcinoma: beta-glucuronidase mediates release of doxorubicin from a glucuronide prodrug (HMR 1826) at the tumor site. Cancer Res., 57: 2440-2445, 1997.
    
    52. Bosslet, K., Straub, R., Blumrich, M, Czech, J., Gerken, M., Sperker, B., Kroemer, H. K., Gesson, J. P., Koch, M., and Monneret, C. Elucidation of the mechanism enabling tumor selective prodrug monotherapy. Cancer Res., 58: 1195-1201, 1998.
    
    53. Platel, D., Bonoron-Adele, S., Dix, R. K., and Robert, J. Preclinical evaluation of the cardiac toxicity of HMR-1826, a novel prodrug of doxorubicin. Br.J.Cancer, 81: 24-27, 1999.
    
    54. Weyel, D., Sedlacek, H. H., Muller, R., and Brusselbach, S. Secreted human beta-glucuronidase: a novel tool for gene-directed enzyme prodrug therapy. Gene Ther., 7:224-231,2000.
    
    55. Fonseca, M. J., Storm, G, Hennink, W. E., Gerritsen, W. R., and Haisma, H. J. Cationic polymeric gene delivery of beta-glucuronidase for doxorubicin prodrug therapy. J.Gene Med., 1: 407-414, 1999.
    
    56. Hao, X. K., Liu, J. Y, Yue, Q. H., Wu, G. J., Bai, Y J., and Yin, Y. In vitro and in vivo prodrug therapy of prostate cancer using anti-gamma-Sm-scFv/hCPA fusion protein. Prostate, 66: 858-866, 2006.
    
    57. Thurston, D. E. Nucleic acid targeting: therapeutic strategies for the 21 st century. Br.J.Cancer, 80 Suppl 1: 65-85, 1999.
    
    58. Owens, J. Something old and something new: taking cancer therapy forward. Drug Discov.Today, 6: 1203-1205, 2001.
    
    59. Cox, A. D. Farnesyltransferase inhibitors: potential role in the treatment of cancer. Drugs, 61: 723-732, 2001.
    
    60. Crul, M., de Klerk, G. J., Beijnen, J. H., and Schellens, J. H. Ras biochemistry and farnesyl transferase inhibitors: a literature survey. Anticancer Drugs, 12: 163-184, 2001.
    
    61. McCawley, L. J. and Matrisian, L. M. Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol.Med.Today, 6: 149-156, 2000.
    
    62. Zwick, E., Bange, J., and Ullrich, A. Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr.Relat Cancer, 8: 161-173,2001.
    
    63. van den Elsen, J. M., Kuntz, D. A., and Rose, D. R. Structure of Golgi alpha-mannosidase II: a target for inhibition of growth and metastasis of cancer cells. EMBO J., 20: 3008-3017, 2001.
    
    64. Rasmussen, H. S. and McCann, P. P. Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol.Ther., 75: 69-75, 1997.
    
    65. Stella, M., De Nardi, P., Paganelli, G, Magnani, P., Mangili, F., Sassi, I., Baratti, D., Gini, P., Zito, R, Cristallo, M., and . Avidin-biotin system in radioimmunoguided surgery for colorectal cancer. Advantages and limits. Dis.Colon Rectum, 37: 335-343, 1994.
    
    66. Fang, H., Peng, S., Chen, A., Li, F., Ren, K., and Hu, N. Biocompatibility studies on fibrin glue cultured with bone marrow mesenchymal stem cells in vitro. J.Huazhong.Univ Sci.Technolog.Med.Sci., 24: 272-274, 2004.
    
    67. Rusetskii, A. N. and Ruuge, E. K. [Hemodynamic aspects of magnetically-guided drug transport]. Biull.Vsesoiuznogo.Kardiol.Nauchn.Tsentra.AMN.SSSR, 7: 85-90, 1984.
    
    68. Tomizawa, M., Ebara, M., Saisho, H., Sakiyama, S., and Tagawa, M. Irradiation with ultrasound of low output intensity increased chemosensitivity of subcutaneous solid tumors to an anti-cancer agent. Cancer Lett., 173: 31-35, 2001.
    
    69. Arap, W., Pasqualini, R., and Ruoslahti, E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science, 279: 377-380, 1998.
    
    70. Recent patents in phage display. Nat.Biotechnol., 18: 1321, 2000.
    
    71. Santamaria, H. [Phage display applications in clinical diagnosis]. Rev.Invest Clin., 55: 711-718,2003.
    
    72. O'Neil, K. T. and Hoess, R. H. Phage display: protein engineering by directed evolution. Curr.Opin.Struct.Biol., 5: 443-449, 1995.
    
    
    73. Rhyner, C, Kodzius, R., and Crameri, R. Direct selection of cDNAs from filamentous phage surface display libraries: potential and limitations. Curr.Pharm.Biotechnol., 3: 13-21, 2002.
    
    74. Kotz, J. D., Bond, C. J., and Cochran, A. G. Phage-display as a tool for quantifying protein stability determinants. Eur.J.Biochem., 271: 1623-1629, 2004.
    
    75. Bustamante, C, Marko, J. F., Siggia, E. D., and Smith, S. Entropic elasticity of lambda-phage DNA. Science, 265: 1599-1600, 1994.
    
    76. Bustamante, C, Marko, J. F., Siggia, E. D., and Smith, S. Entropic elasticity of lambda-phage DNA. Science, 265: 1599-1600, 1994.
    
    77. Maruyama, I. N., Maruyama, H. I., and Brenner, S. Lambda foo: a lambda phage vector for the expression of foreign proteins. Proc.Natl.Acad.Sci.U.S.A, 91: 8273-8277, 1994.
    
    78. Bustamante, C, Marko, J. F., Siggia, E. D., and Smith, S. Entropic elasticity of lambda-phage DNA. Science, 265: 1599-1600, 1994.
    
    79. Maruyama, I. N., Maruyama, H. I., and Brenner, S. Lambda foo: a lambda phage vector for the expression of foreign proteins. Proc.Natl.Acad.Sci.U.S.A, 91: 8273-8277, 1994.
    
    80. Muniyappa, K. and Mythili, E. Phage lambda beta protein, a component of general recombination, is associated with host ribosomal S1 protein. Biochem.Mol.Biol.Int., 31: 1-11, 1993.
    
    81. Yonesaki, T. Recombination apparatus of T4 phage. Adv.Biophys., 31: 3-22, 1995.
    
    82. Cooper, W. G. T4 phage evolution data in terms of a time-dependent Topal-Fresco mechanism. Biochem.Genet., 32: 383-395, 1994.
    
    83. Hintermann, E. and Kuhn, A. Bacteriophage T4 gene 21 encodes two proteins essential for phage maturation. Virology, 189: 474-482, 1992.
    
    84. Mosig, G The essential role of recombination in phage T4 growth. Annu.Rev.Genet., 21: 347-371, 1987.
    
    85. Black, L. W. In vitro packaging into phage T4 particles and specific recircularization of phage lambda DNAs. Gene, 46: 97-101, 1986.
    
    86. Nowak, J. E., Chatterjee, M., Mohapatra, S., Dryden, S. C, and Tainsky, M. A. Direct production and purification of T7 phage display cloned proteins selected and analyzed on microarrays. Biotechniques, 40: 220-227, 2006.
    
    87. Takakusagi, Y., Ohta, K., Kuramochi, K., Morohashi, K., Kobayashi, S., Sakaguchi, K., and Sugawara, F. Synthesis of a biotinylated camptothecin derivative and determination of the binding sequence by T7 phage display technology. Bioorg.Med.Chem.Lett., 15: 4846-4849, 2005.
    
    88. Danner, S. and Belasco, J. G. T7 phage display: a novel genetic selection system for cloning RNA-binding proteins from cDNA libraries. Proc.Natl.Acad.Sci.U.S.A, 98: 12954-12959,2001.
    
    89. Du, B., Qian, M., Zhou, Z., Wang, P., Wang, L., Zhang, X., Wu, M., Zhang, P., and Mei, B. In vitro panning of a targeting peptide to hepatocarcinoma from a phage display peptide library. Biochem.Biophys.Res.Commun., 342: 956-962, 2006.
    
    90. Du, B., Yu, J., Zhou, Z. L., Zhang, P., Yu, M., and Qian, M. [Selection of the peptides specifically binding to hepatoma by using phage display in vivo]. Zhonghua Zhong.Liu Za Zhi., 27: 645-647, 2005.
    
    1. Zampieri, S., Mahler, M., Bluthner, M., Qiu, Z., Mahnegrim, K., Ghirardello, A., Doria, A., van Venrooij, W. J., and Raats, J. M. Recombinant anti-P protein autoantibodies isolated from a human autoimmune library: reactivity, specificity and epitope recognition. Cell Mol. Life Sci., 60: 588-598, 2003.
    2. Watanabe, H., Tsumoto, K., Asano, R., Nishimiya, Y., and Kumagai, I. Selection of human antibody fragments on the basis of stabilization of the variable domain in the presence of target antigens. Biochem. Biophys. Res. Commun., 295: 31-36, 2002.
    3. Jung, S., Arndt, K. M., Muller, K. M., and Pluckthun, A. Selectively infective phage (SIP) technology: scope and limitations. J.Immunol. Methods, 231: 93-104, 1999.
    4. Raats, J., van Bree, N., van Woezik, J., and Pruijn, G. Generating recombinant anti-idiotypic antibodies for the detection of haptens in solution. J. Immunoassay Immunochem., 24: 115-146, 2003.
    5. Hombach, A., Pohl, C., Heuser, C., Sircar, R., Diehl, V., and Abken, H. Isolation of single chain antibody fragments with specificity for cell surface antigens by phage display utilizing internal image anti-idiotypic antibodies. J.Immunol.Methods, 218: 53-61, 1998.
    6. Hoogenboom, H. R., de Bruine, A. P., Hufton, S. E., Hoet, R. M., Arends, J. W., and Roovers, R. C. Antibody phage display technology and its applications. Immunoteehnology., 4: 1-20, 1998.
    7. Du, B., Qian, M., Zhou, Z., Wang, P., Wang, L., Zhang, X., Wu, M., Zhang, P., and Mei, B. In vitro panning of a targeting peptide to hepatocarcinoma from a phage display peptide library. Biochem. Biophys. Res. Commun., 342: 956-962, 2006.
    8. Gao, C., Mao, S., Ditzel, H. J., Farnaes, L., Wirsching, P., Lerner, R. A., and Janda, K. D. A cell-penetrating peptide from a novel pⅦ-pⅨ phage-displayed random peptide library. Bioorg. Med. Chem., 10: 4057-4065, 2002.
    9. Zhu, J. G., Hu, J. Y., and Li, G. C. [Primary characterization and sequence analysis of anti-colorectal cancer phage fusion antibodies]. Hunan. Yi. Ke. Da. Xue. Xue. Bao., 27: 95-98, 2002.
    10. Du, B., Yu, J., Zhou, Z. L., Zhang, P., Yu, M., and Qian, M. [Selection of the peptides specifically binding to hepatoma by using phage display in vivo]. Zhonghua Zhong. Liu Za Zhi., 27: 645-647. 2005.
    11. Trepel, M., Arap, W., and Pasqualini, R. In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr. Opin. Chem. Biol., 6: 399-404, 2002.
    12. Okazaki, K., Nakayama, Y., Shibao, K., Hirata, K., Sako, T., Nagata, N., Kuroda, Y., and Itoh, H. Establishment of a human colon cancer cell line (PMF-kol4) displaying highly metastatic activity. Int. J. Oncol., 17: 39-45, 2000.
    13. Arap, W., Pasqualini, R., and Ruoslahti, E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science, 279: 377-380, 1998.
    14. Fatehi, A. N., van den, H. R., Colenbrander, B., Daemen, A. J., van Tol, H. T., Monteiro, R. M., Roelen, B. A., and Bevers, M. M. Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IV M on bovine oocyte nuclear??maturation and subsequent embryo development. Theriogenology, 63: 872-889, 2005.
    15. Arap, W., Kolonin, M. G., Trepel, M., Lahdenranta, J., Cardo-Vila, M., Giordano, R. J., Mintz, P. J., Ardelt, P. U., Yao, V. J., Vidal, C. I., Chen, L., Flamm, A., Valtanen, H., Weavind, L. M., Hicks, M. E., Pollock, R. E., Botz, G. H., Bucana, C. D., Koivunen, E., Cahill, D., Troncoso, P., Baggerly, K. A., Pentz, R. D., Do, K. A., Logothetis, C. J., and Pasqualini, R. Steps toward mapping the human vasculature by phage display. Nat. Med., 8: 121-127, 2002.
    16. Cooke, S. P., Boxer, G. M., Lawrence, L., Pedley, R. B., Spencer, D. I., Begent, R. H., and Chester, K. A. A strategy for antitumor vascular therapy by targeting the vascular endothelial growth factor: receptor complex. Cancer Res., 61: 3653-3659, 2001.
    17. Li, Z. Q., Shi, Z. J., Hao, W. B., and L H Establishment of biopanning model of phage display peptide library in the blood vessels of excised human osteosarcoma vasculature and its significance. Di Yi. Jun. Yi. Da. Xue. Xue. Bao., 22: 212-214, 2002.
    18. Smith, G. P. and Petrenko, V. A. Phage Display. Chem. Rev., 97: 391-410, 1997.
    19. Smith, G. P. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science, 228: 1315-1317, 1985.1. Prasher, D. C, Eckenrode, V. K., Ward, W. W., Prendergast, F. G, and Cormier, M. J. Primary structure of the Aequorea victoria green-fluorescent protein. Gene, 111: 229-233, 1992.
    
    2. Cody, C. W., Prasher, D. C, Westler, W. M, Prendergast, F. G, and Ward, W. W. Chemical structure of the hexapeptide chromophore of the Aequorea green-fluorescent protein. Biochemistry, 32: 1212-1218, 1993.
    
    3. Heim, R., Cubitt, A. B., and Tsien, R. Y. Improved green fluorescence. Nature, 373: 663-664, 1995.
    
    4. Stearns, T. Green fluorescent protein. The green revolution. Curr.Biol., 5: 262-264, 1995.
    
    5. Cormack, B. P., Valdivia, R. H., and Falkow, S. FACS-optimized mutants of the green fluorescent protein (GFP). Gene, 173: 33-38,1996.
    
    6. Zolotukhin, S., Potter, M., Hauswirth, W. W., Guy, J., and Muzyczka, N. A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J.Virol., 70: 4646-4654,1996.
    
    7. Heim, R., Cubitt, A. B., and Tsien, R. Y. Improved green fluorescence. Nature, 373: 663-664, 1995.
    
    8. Heim, R., Prasher, D. C, and Tsien, R. Y. Wavelength mutations and posttranslational autoxidation of green fluorescent protein. Proc.Natl.Acad.Sci.U.S.A, 91: 12501-12504, 1994.
    
    9. Ward, W. W. and Bokman, S. H. Reversible denaturation of Aequorea green-fluorescent protein: physical separation and characterization of the renatured protein. Biochemistry, 21: 4535-4540, 1982.
    
    10. Cubitt, A. B., Heim, R., Adams, S. R., Boyd, A. E., Gross, L. A., and Tsien, R. Y. Understanding, improving and using green fluorescent proteins. Trends Biochem.Sci., 20: 448-455, 1995.
    
    11. Coxon, A. and Bestor, T. H. Proteins that glow in green and blue. Chem.Biol., 2: 119-121,1995.
    
    12. Goodell, V. and Disis, M. L. Human tumor cell lysates as a protein source for the detection of cancer antigen-specific humoral immunity. J.Immunol.Methods, 299: 129-138,2005.
    
    13. Nowakowski, G S., Dooner, M. S., Valinski, H. M., Mihaliak, A. M, Quesenberry, P. J., and Becker, P. S. A specific heptapeptide from a phage display peptide library homes to bone marrow and binds to primitive hematopoietic stem cells. Stem Cells, 22: 1030-1038,2004.
    
    14. Michon, I. N., Hauer, A. D., der Thusen, J. H., Molenaar, T. J., van Berkel, T. J., Biessen, E. A., and Kuiper, J. Targeting of peptides to restenotic vascular smooth muscle cells using phage display in vitro and in vivo. Biochim.Biophys.Acta, 1591: 87-97, 2002.
    
    15. Lee, Y. J., Kim, D. H., Kim, Y. W., and Hwang, I. Identification of a signal that distinguishes between the chloroplast outer envelope membrane and the endomembrane system in vivo. Plant Cell, 13: 2175-2190, 2001.
    
    16. McCloskey, K. E., Zborowski, M., and Chalmers, J. J. Measurement of CD2 expression levels of IFN-alpha-treated fibrosarcomas using cell tracking velocimetry. Cytometry, 44: 137-147,2001.
    
    17. Chen, X., Liu, Z., and Ai, Z. Antineoplastic mechanism of Octreotide action in human hepatoma. Chin Med.J.(Engl), 114: 1167-1170, 2001.
    
    18. Bjork, P., Jonsson, U., Svedberg, H., Larsson, K., Lind, P., Dillner, J., Hedlund, G, Dohlsten, M., and Kalland, T. Isolation, partial characterization, and molecular cloning of a human colon adenocarcinoma cell-surface glycoprotein recognized by the C215 mouse monoclonal antibody. J.Biol.Chem., 268: 24232-24241, 1993.
    
    19. Wojnar, P., Lechner, M., Merschak, P., and Redl, B. Molecular cloning of a novel lipocalin-1 interacting human cell membrane receptor using phage display.??J. Biol. Chem., 276: 20206-20212, 2001.
    20. Wu, X., Zhao, R., Li, Z., Yao, M., Wang, H., Han, J., Qu, S., Chen, X., Qian, L., Sun, Y., Xu, Y., and Gu, J. A novel small peptide as a targeting ligand for receptor tyrosine kinase Tie2. Biochem. Biophys. Res. Commun., 315: 1004-1010, 2004.
    21. Hetian, L., Ping, A., Shumei, S., Xiaoying, L., Luowen, H., Jian, W., Lin, M., Meisheng, L., Junshan, Y., and Chengchao, S. A novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to its kinase domain receptor. J. Biol. Chem., 277: 43137-43142, 2002.
    22. Rajarao, G. K., Nekhotiaeva, N., and Good, L. The signal peptide NPFSD fused to ricin A chain enhances cell uptake and cytotoxicity in Candida albicans. Biochem. Biophys. Res. Commun., 301: 529-534, 2003.1. Johannsen, M., Thiesen, B., Jordan, A., Taymoorian, K., Gneveckow, U., Waldofner, N., Scholz, R., Koch, M., Lein, M., Jung, K., and Loening, S. A. Magnetic fluid hyperthermia (MFH)reduces prostate cancer growth in the orthotopic Dunning R3327 rat model. Prostate, 64: 283-292, 2005.
    
    2. Raikher, I., Shliomis, M. I., and Frank, V. A. [Use of magnetic fluids in clinical medicine]. Klin.Khir., 73-74,1988.
    
    3. Barybin, A. S. and Reshchikov, V. P. [Use of permanent magnets and magnetic fluids in experimental oncology]. Eksp.Onkol., 7: 18-22, 71, 1985.
    
    4. Gunther, D. [Tumor diagnosis, therapy and drug targeting with magnetic fluids]. Pharm.Unserer Zeit, 25: 130-134,1996.
    
    5. Sugibayashi, K., Okumura, M, and Morimoto, Y. Biomedical applications of magnetic fluids. III. Antitumour effect of magnetic albumin microsphere-entrapped adriamycin on lung metastasis of AH 7974 in rats. Biomaterials, 3: 181-186, 1982.
    
    6. Morimoto, Y, Okumura, M., Sugibayashi, K., and Kato, Y Biomedical applications of magnetic fluids II. 1) preparation and magnetic guidance of magnetic albumin microsphere for site specific drug delivery in vivo. J.Pharmacobiodyn., 4: 624-631,1981.
    
    7. Morimoto, Y, Sugibayashi, K., Okumura, M., and Kato, Y Biomedical applications of magnetic fluids, i. Magnetic guidance of ferro-colloid-entrapped albumin microsphere for site specific drug delivery in vivo. J.Pharmacobiodyn., 3: 264-267,1980.
    
    8. Jordan, A., Scholz, R., Maier-Hauff, K., van Landeghem, F. K., Waldoefner, N., Teichgraeber, U., Pinkernelle, J., Bruhn, H., Neumann, F., Thiesen, B., von Deimling, A., and Felix, R. The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J.Neurooncol., 1-8,2005.
    
    9. Johannsen, M., Thiesen, B., Jordan, A., Taymoorian, K., Gneveckow, U., Waldofner, N., Scholz, R., Koch, M., Lein, M., Jung, K., and Loening, S. A. Magnetic fluid hyperthermia (MFH)reduces prostate cancer growth in the orthotopic Dunning R3327 rat model. Prostate, 64: 283-292, 2005.
    
    10. Jordan, A., Scholz, R., Maier-Hauff, K., van Landeghem, F. K., Waldoefner, N., Teichgraeber, U., Pinkernelle, J., Bruhn, H., Neumann, F., Thiesen, B., von Deimling, A., and Felix, R. The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J.Neurooncol., 1-8,2005.
    
    11. Johannsen, M., Gneveckow, U., Eckelt, L., Feussner, A., Waldofner, N., Scholz, R., Deger, S., Wust, P., Loening, S. A., and Jordan, A. Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique. Int.J.Hyperthermia, 21: 637-647,2005.
    
    12. Babincova, M., Sourivong, P., Leszczynska, D., and Babinec, P. Blood-specific whole-body electromagnetic hyperthermia. Med.Hypotheses, 55: 459-460,2000.
    
    13. Alexiou, C, Jurgons, R., Schmid, R. J., Bergemann, C, Henke, J., Erhardt, W., Huenges, E., and Parak, F. Magnetic drug targeting-biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment. J.Drug Target, 11: 139-149, 2003.
    
    14. Gunther, D. [Tumor diagnosis, therapy and drug targeting with magnetic fluids]. Pharm.Unserer Zeit, 25: 130-134,1996.
    
    15. Sugibayashi, K., Okumura, M., and Morimoto, Y Biomedical applications of??magnetic fluids. Ⅲ. Antitumour effect of magnetic albumin microsphere-entrapped addamycin on lung metastasis of AH 7974 in rats. Biomaterials, 3: 181-186, 1982.
    16. Morimoto, Y., Okumura, M., Sugibayashi, K., and Kato, Y. Biomedical applications of magnetic fluids Ⅱ. 1) preparation and magnetic guidance of magnetic albumin microsphere for site specific drug delivery in vivo. J. Pharmacobiodyn., 4: 624-631, 1981.
    17. Morimoto, Y., Sugibayashi, K., Okumura, M., and Kato, Y. Biomedical applications of magnetic fluids, i. Magnetic guidance of ferro-colloid-entrapped albumin microsphere for site specific drug delivery in vivo. J. Pharmacobiodyn., 3: 264-267, 1980.
    18. Viola, A., Chabrol, B., Nicoli, F., Confort-Gouny, S., Viout, P., and Cozzone, P. J. Magnetic resonance spectroscopy study of glycine pathways in nonketotic hyperglycinemia. Pediatr. Res., 52: 292-300, 2002.
    19. Traore, A. S., Woerly, S., Doan, V. D., Marois, Y., and Guidoin, R. In vivo magnetic resonance imaging and relaxometry study of a porous hydrogel implanted in the trapezius muscle of rabbits. Tissue Eng, 6: 265-278, 2000.
    20. Laing, A. D. and Gibson, R. N. Magnetic resonance cholangiopancreatography. Australas. Radiol., 43: 284-293, 1999.
    21. Ma, X., Gullberg, G. T., and Parker, D. L. Magnetic resonance imaging verification of a multi-compartment perfusion model for a chromatography gel phantom. Magn Reson. Imaging, 13: 581-598, 1995.
    22. Tanghe, H. L. Magnetic resonance imaging (MRI) in syringomyelia. Acta Neurochir.(Wien.), 134: 93-99, 1995.
    23. Smith, I. C. and Blandford, D. E. Nuclear magnetic resonance spectroscopy. Anal. Chem., 67: 509R-518R, 1995.
    24. Parker, D. L., Parker, D. J., Blatter, D. D., Du, Y. E, and Goodrich, K. C. The effect of image resolution on vessel signal in high-resolution magnetic resonance angiography. J.Magn Reson. Imaging, 6: 632-641, 1996.
    25. Cozzone, P. J., Vion-Dury, J., Bendahan, D., and Confort-Gouny, S. [Future path of magnetic resonance spectroscopy in clinical medicine]. Rev. Prat., 46: 853-858, 1996.
    26. McCarthy, M. J. and McCarthy, K. L. Applications of magnetic resonance imaging to food research. Magn Reson. Imaging, 14: 799-802, 1996.[1] Kohler G Milstein C,Continuous cultures of fused cells secreting antibody of predefined specificity. Nature,l975;256:495
    [2] Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR.Making antibodies by phage display technology. Ann. Revlmmunol 1994 ; 12 : 433-55.
    [3] de Haard H, Henderikx P, Hoogenboom H. Creating and engineering human antibodies for immunotherapy. Adv Drug Delivery Rev 1998 ; 31 : 5-31.] [ Barbas C, Burton D, Silverman G, Scott J, Eds. Phage display of proteins and peptides: a laboratory manual. Cold Spring Harbor: Cold Spring Harbor Press; 2000.
    [4] Tsui P, Tornetta MA, Ames RS. Progressive epitope-blocked panning of a phage library for isolation of human RSV antibodies. J Immunol Methods 2002 May l;263(l-2): 123-32.
    [5] Chang TY, Siegel DL.Genetic and immunological properties of phage-displayed human anti-Rh(D) antibodies: implications for Rh(D) epitope topology. Blood 1998 ; 91 : 3066-78.
    [6] Miescher S, Vogel M, Biaggi C, Ramseyer V, Hustinx H, Eicher N, et al. Sequence and specificity analysis of recombinant human Fab anti-Rh D isolated by phage display. Vox Sang 1998 ; 75 : 278-87.
    
    [7] Miescher S, Zahn-Zabal M, De Jesus M, Moudry R, Fisch I, Vogel M, et al. CHO expression of a novel human recombinant IgG1 anti-RhD antibody isolated by phage display. Br J Haematol 2000; 111 : 157-66.
    [8] Chang TY, Siegel DL. Isolation of an IgG anti-B from a human Fab-phage display library. Transfusion 2001 ; 41 : 6-12.
    
    [9] Kollnberger SD, Gutierrez-Castaneda B, Foster-Cuevas M,et al. Identification of the principal serological immunodeterminants of African swine fever virus by screening a virus cDNA library with antibody. J Gen Virol 2002 Jun;83(Pt 6):1331-42
    
    [10] Zhou B, Wirsching P, Janda KD. Human antibodies against spores of the genus Bacillus: A model study for detection of and protection against anthrax and the bioterrorist threat. Proc Natl Acad Sci U S A2002 Apr 16;99(8):5241-6
    
    [11] Hughes-Jones NC, Bye JM, Gorick BD, Marks JD, Ouwehand WH. Synthesis of Rh Fv phage-antibodies using VH and VL germline genes. Br J Haematol 1999 ; 105 : 811-6.
    [12] Karl Kramer,Markus Fiedler, Arne Skerra,et al. A generic strategy for subcloning antibody variable regions from the scFv phage display vector pCANTAB 5 E into pASK85 permits the economical production of Fab fragments and leads to improved recombinant immunoglobulin stability. Biosensors & Bioelectronics 17 (2002) 305-313
    
    [13] Czerwinski M, Siemaszko D, Siegel DL, Spitalnik SL. Only selected light chains combine with a given heavy chain to confer specificity for a model glycopeptide antigen. J Immunol 1998 ; 160 : 4406-17.
    
    [14] Czerwinski M, Krop-Watorek A, Siegel DL, Spitalnik SL. A molecular approach for isolating high-affinity Fab fragments that are useful in blood group serology. Transfusion 1999 ; 39 : 364-71.
    [15] Siegel DL. Research and clinical applications of antibody phage display in transfusion medicine. Transfus Med Rev 2001 ; 15 : 35-52.
    [16] Siegel DL, Chang TY. Epitope migration: Anti-Rh(D) antibodies as amodel for human immunogenicity. Blood 1998 ; 92 : 671a.
    [17] G Strachan,J. McElhiney ,M.R. Drever. Rapid selection of anti-hapten antibodies isolated fromsynthetic and semi-synthetic antibody phage display libraries expressed in Escherichia coli FEMS Microbiology Letters 10452 (2002) 1 -5
    [18] Siegel DL, Chang TY, Russell SL, Bunya VY. Isolation of cell surface-specific human monoclonal antibodies using phage display and magnetically-activated cell sorting: applications in immunohematology. J Immunol Methods 1997 ; 206 : 73-85.
    [19] Siegel DL, Silberstein LE. Expression and characterization of recombinant anti-Rh(D) antibodies on filamentous phage: a model system for isolating human red blood cell antibodies by repertoire cloning. Blood 1994 ; 83 : 2334-44.
    [20] Hughes-Jones NC, Gorick BD, Bye JM, Finnern R, Scott ML, Voak D, et al. Characterization of human blood group scFv antibodies derived from a V gene phage-display library. Br J Haematol 1994; 88: 180-6.
    [21] Furuta M, Uchikawa M, Ueda Y, Yabe T, Taima T, Tsumoto K, et al. Construction of mono- and bivalent human single-chain Fv fragments against theDantigen in the Rh blood group: multimerization effect on cell agglutination and application to blood typing. Prot Eng 1998 ; 11 : 233-41.
    [22] Libyh MT, Goossens D, Oudin S, Gupta N, Dervillez X, Juszczak G, et al. A recombinant human scFv anti-Rh(D) antibody with multiple valences using a C-terminal fragment of C4-binding protein. Blood 1997 ; 90 : 3978-83.
    [23] Watkins NA, Armour KL, Smethurst PA, Metcalfe P, Scott ML, Hughes DL, et al. Rapid phenotyping of HPA-la using either diabody-based hemagglutination or recombinant IgG1-based assays. Transfusion 1999 ; 39 : 781-9.
    [24] Sanna PP, Samson ME, Moon JS, Rozenshteyn R, De Logu A,Williamson RA, et al. pFab-CMV, a single vector system for the rapid conversion of recombinant Fabs into whole IgG1 antibodies. Immunotechnol 1999 ; 4 : 185-8.
    [25] Kumpel BM, Goodrick MJ, Pamphilon DH, Fraser ID,Poole GD, Morse C, et al. Human RhDmonoclonal antibodies BRAD-3 and BRAD-5] cause accelerated clearance of Rh D+ red blood cells and suppression of RhDimmunization in Rh Dvolunteers. Blood 1995 ; 86 : 1701-9.
    [26] Miescher S, Zahn-Zabal M, De Jesus M, Moudry R, Fisch Vogel M, et al. CHO expression of a novel human recombinant IgG1 anti-RhD antibody isolated by phage display. Br J Haematol 2000 ; 111 : 157-66.
    [27] Roark JH, Chang TY, Caton M, Siegel DL. Isolation of human IgG platelet autoantibodies using phage display. Transfusion 1998 ; 38 : 1S.
    [28] Jendreyko N, Uttenreuther-Fischer MM, Lerch H, Gaedicke G, Fischer P. Genetic origin of IgG antibodies cloned by phage display and anti-idiotypic panning from three patients with autoimmune thrombocytopenia. Eur J Immunol 1998; 28: 4236-47.
    [29] Fischer P, Jendreyko N, Hoffmann M, Lerch H, Uttenreuther-Fischer MM, Chen PP, et al. Platelet-reactive IgG antibodiescloned by phage display and panning with IVIG from three patients with autoimmune thrombocytopenia. Br J Haematol .1999 ; 105 : 626-40.
    [30] Armour KL, Clark MR, Hadley AG, Williamson LM. Recombinant human IgG molecules lacking Fcgamma receptor I binding and monocyte triggering activities. Eur J Immunol 1999 ; 29 : 2613-24.

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