Phage Display as A Bio-Technique for Cancer Immunotherapy

Shirin       Mahmoodi; Navid       Nezafat; Younes       Ghasemi
Abstract

Background: Phage display is a biotechnological technique that presents peptides with coated proteins on the surface of phage. In the last two decades, growing applications of phage display in various fields of biotechnology have been investigated. Phage display libraries allow to present billions of peptides on phage surface for selection of a specific peptide with the desired affinity.
Objective: In this regard, high-affinity phage antibodies against tumor antigens are produced and applied for diagnosis and treatment of cancer.
Methods: Moreover, phage display libraries are employed to select the high affinity T Cell Receptors (TCRs) for the peptide-MHC complex which is an attractive approach in cancer immunotherapy. Due to immunogenic properties of phage particles, phage-based vaccines do not require adjuvant, in addition the phage particles can effectively take up by Antigen Presenting Cells (APCs).
Results: Taken together, phage-based cancer vaccines are ideal candidates that provide a key for eradication of tumor cells.
Conclusion: In this review, we focus on various applications of a phage display platform in different types of cancer immunotherapy approaches.
Keywords: Phage display, affinity, antibody, vaccine, cancer, immunotherapy.
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[1] 
Shariat, S.; Badiee, A.; Jalali, S.A.; Mansourian, M.; Yazdani, M.; Mortazavi, S.A.; Jaafari, M.R. P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer. Cancer Lett.,  2014, 355(1), 54-60.
[http://dx.doi.org/10.1016/j.canlet.2014.09.016] [PMID:  25224570] 
[2] 
Blattman, J.N.; Greenberg, P.D. Cancer immunotherapy: A treatment for the masses. Science,  2004, 305(5681), 200-205.
[http://dx.doi.org/10.1126/science.1100369] [PMID:  15247469] 
[3] 
Dougan, M.; Dranoff, G. Innate immune regulation and cancer immunotherapy.,  2012, 391-414.
[http://dx.doi.org/10.1007/978-1-4419-9914-6_22] 
[4] 
Lesterhuis, W.J.; Haanen, J.B.; Punt, C. J. Cancer immunotherapy-revisited. Nat. Rev. Drug Discov.,  2011, 10(8), 591-600.
[http://dx.doi.org/10.1038/nrd3500] [PMID:  21804596] 
[5] 
Vergati, M.; Intrivici, C.; Huen, N-Y.; Schlom, J.; Tsang, K.Y. Strategies for cancer vaccine development. J. Biomed. Biotechnol., 2010. 596432
[http://dx.doi.org/10.1155/2010/596432] [PMID:  20706612] 
[6] 
Sergeeva, A.; Kolonin, M.G.; Molldrem, J.J.; Pasqualini, R.; Arap, W. Display technologies: Application for the discovery of drug and gene delivery agents. Adv. Drug Deliv. Rev.,  2006, 58(15), 1622-1654.
[http://dx.doi.org/10.1016/j.addr.2006.09.018] [PMID:  17123658] 
[7] 
Leemhuis, H.; Stein, V.; Griffiths, A.D.; Hollfelder, F. New genotype-phenotype linkages for directed evolution of functional proteins. Curr. Opin. Struct. Biol.,  2005, 15(4), 472-478.
[http://dx.doi.org/10.1016/j.sbi.2005.07.006] [PMID:  16043338] 
[8] 
Tateyama, S.; Horisawa, K.; Takashima, H.; Miyamoto-Sato, E.; Doi, N.; Yanagawa, H. Affinity selection of DNA-binding protein complexes using mRNA display. Nucleic Acids Res.,  2006, 34(3), e27-e27.
[http://dx.doi.org/10.1093/nar/gnj025] [PMID:  16478713] 
[9] 
Pande, J.; Szewczyk, M.M.; Grover, A.K. Phage display: Concept, innovations, applications and future. Biotechnol. Adv.,  2010, 28(6), 849-858.
[http://dx.doi.org/10.1016/j.biotechadv.2010.07.004] [PMID:  20659548] 
[10] 
Sidhu, S.S. Engineering M13 for phage display. Biomol. Eng.,  2001, 18(2), 57-63.
[http://dx.doi.org/10.1016/S1389-0344(01)00087-9] [PMID:  11535417] 
[11] 
Chaput, J.C.; Szostak, J.W. Evolutionary optimization of a nonbiological ATP binding protein for improved folding stability. Chem. Biol.,  2004, 11(6), 865-874.
[http://dx.doi.org/10.1016/j.chembiol.2004.04.006] [PMID:  15217619] 
[12] 
Kurz, M.; Gu, K.; Al-Gawari, A.; Lohse, P.A. cDNA - protein fusions: Covalent protein - gene conjugates for the in vitro selection of peptides and proteins. ChemBioChem,  2001, 2(9), 666-672.
[http://dx.doi.org/10.1002/1439-7633(20010903)2:9<666:AID-CBIC666>3.0.CO;2-#] [PMID:  11828503] 
[13] 
Cochran, F.V.; Wu, S.P.; Wang, W.; Nanda, V.; Saven, J.G.; Therien, M.J.; DeGrado, W.F. Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. J. Am. Chem. Soc.,  2005, 127(5), 1346-1347.
[http://dx.doi.org/10.1021/ja044129a] [PMID:  15686346] 
[14] 
Bertschinger, J.; Neri, D. Covalent DNA display as a novel tool for directed evolution of proteins in vitro. Protein Eng. Des. Sel.,  2004, 17(9), 699-707.
[http://dx.doi.org/10.1093/protein/gzh082] [PMID:  15522920] 
[15] 
Bradbury, A.R.; Marks, J.D. Antibodies from phage antibody libraries. J. Immunol. Methods,  2004, 290(1-2), 29-49.
[http://dx.doi.org/10.1016/j.jim.2004.04.007] [PMID:  15261570] 
[16] 
Bazan, J.; Całkosiński, I.; Gamian, A. Phage display--a powerful technique for immunotherapy: 1. Introduction and potential of therapeutic applications. Hum. Vaccin. Immunother.,  2012, 8(12), 1817-1828.
[http://dx.doi.org/10.4161/hv.21703] [PMID:  22906939] 
[17] 
Jakobsen, C.G.; Rasmussen, N.; Laenkholm, A-V.; Ditzel, H.J. Phage display derived human monoclonal antibodies isolated by binding to the surface of live primary breast cancer cells recognize GRP78. Cancer Res.,  2007, 67(19), 9507-9517.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4686] [PMID:  17909061] 
[18] 
Dantas-Barbosa, C.; de Macedo Brigido, M.; Maranhao, A.Q. Antibody phage display libraries: Contributions to oncology. Int. J. Mol. Sci.,  2012, 13(5), 5420-5440.
[http://dx.doi.org/10.3390/ijms13055420] [PMID:  22754305] 
[19] 
Smith, G.P. Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface. Science,  1985, 228(4705), 1315-1317.
[http://dx.doi.org/10.1126/science.4001944] [PMID:  4001944] 
[20] 
Qi, H.; Lu, H.; Qiu, H-J.; Petrenko, V.; Liu, A. Phagemid vectors for phage display: Properties, characteristics and construction. J. Mol. Biol.,  2012, 417(3), 129-143.
[http://dx.doi.org/10.1016/j.jmb.2012.01.038 ] [PMID:  22310045] 
[21] 
Huang, J.; Ru, B.; Dai, P. Bioinformatics resources and tools for phage display. Molecules,  2011, 16(1), 694-709.
[http://dx.doi.org/10.3390/molecules16010694] [PMID:  21245805] 
[22] 
Sidhu, S.S. Phage display in pharmaceutical biotechnology. Curr. Opin. Biotechnol.,  2000, 11(6), 610-616.
[http://dx.doi.org/10.1016/S0958-1669(00)00152-X] [PMID:  11102798] 
[23] 
Haq, I.U.; Chaudhry, W.N.; Akhtar, M.N.; Andleeb, S.; Qadri, I. Bacteriophages and their implications on future biotechnology: A review. Virol. J.,  2012, 9(1), 9.
[http://dx.doi.org/10.1186/1743-422X-9-9] [PMID:  22234269] 
[24] 
Wilson, D.R.; Finlay, B.B. Phage display: Applications, innovations, and issues in phage and host biology. Can. J. Microbiol.,  1998, 44(4), 313-329.
[http://dx.doi.org/10.1139/w98-015] [PMID:  9674105] 
[25] 
Bratkovič, T. Progress in phage display: Evolution of the technique and its application. Cell. Mol. Life Sci.,  2010, 67(5), 749-767.
[http://dx.doi.org/10.1007/s00018-009-0192-2] [PMID:  20196239] 
[26] 
Paschke, M. Phage display systems and their applications. Appl. Microbiol. Biotechnol.,  2006, 70(1), 2-11.
[http://dx.doi.org/10.1007/s00253-005-0270-9] [PMID:  16365766] 
[27] 
Georgiou, G.; Stathopoulos, C.; Daugherty, P.S.; Nayak, A.R.; Iverson, B.L.; Curtiss, R., III Display of heterologous proteins on the surface of microorganisms: From the screening of combinatorial libraries to live recombinant vaccines. Nat. Biotechnol.,  1997, 15(1), 29-34.
[http://dx.doi.org/10.1038/nbt0197-29] [PMID:  9035102] 
[28] 
Ebrahimizadeh, W.; Rajabibazl, M. Bacteriophage vehicles for phage display: Biology, mechanism, and application. Curr. Microbiol.,  2014, 69(2), 109-120.
[http://dx.doi.org/10.1007/s00284-014-0557-0] [PMID:  24638925] 
[29] 
Wells, J.A. Systematic mutational analyses of protein-protein interfaces. Methods Enzymol.,  1991, 202, 390-411.
[http://dx.doi.org/10.1016/0076-6879(91)02020-A] [PMID:  1723781] 
[30] 
Knappik, A.; Ge, L.; Honegger, A.; Pack, P.; Fischer, M.; Wellnhofer, G.; Hoess, A.; Wölle, J.; Plückthun, A.; Virnekäs, B. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J. Mol. Biol.,  2000, 296(1), 57-86.
[http://dx.doi.org/10.1006/jmbi.1999.3444] [PMID:  10656818] 
[31] 
Fang, J.; Wang, G.; Yang, Q.; Song, J.; Wang, Y.; Wang, L. The potential of phage display virions expressing malignant tumor specific antigen MAGE-A1 epitope in murine model. Vaccine,  2005, 23(40), 4860-4866.
[http://dx.doi.org/10.1016/j.vaccine.2005.05.024] [PMID:  16029917] 
[32] 
Hudson, P.J. Recombinant antibody constructs in cancer therapy. Curr. Opin. Immunol.,  1999, 11(5), 548-557.
[http://dx.doi.org/10.1016/S0952-7915(99)00013-8] [PMID:  10508712] 
[33] 
Carroll, M.C. The complement system in regulation of adaptive immunity. Nat. Immunol.,  2004, 5(10), 981-986.
[http://dx.doi.org/10.1038/ni1113] [PMID:  15454921] 
[34] 
Aghebati-Maleki, L.; Bakhshinejad, B.; Baradaran, B.; Motallebnezhad, M.; Aghebati-Maleki, A.; Nickho, H.; Yousefi, M.; Majidi, J. Phage display as a promising approach for vaccine development. J. Biomed. Sci.,  2016, 23(1), 66.
[http://dx.doi.org/10.1186/s12929-016-0285-9] [PMID:  27680328] 
[35] 
Knittelfelder, R.; Riemer, A.B.; Jensen-Jarolim, E. Mimotope vaccination--from allergy to cancer. Expert Opin. Biol. Ther.,  2009, 9(4), 493-506.
[http://dx.doi.org/10.1517/14712590902870386] [PMID:  19344285] 
[36] 
Olszewska, W.; Obeid, O.E.; Steward, M.W. Protection against measles virus-induced encephalitis by anti-mimotope antibodies: The role of antibody affinity. Virology,  2000, 272(1), 98-105.
[http://dx.doi.org/10.1006/viro.2000.0285] [PMID:  10873752] 
[37] 
Ho, P.C.; Mutch, D.A.; Winkel, K.D.; Saul, A.J.; Jones, G.L.; Doran, T.J.; Rzepczyk, C.M. Identification of two promiscuous T cell epitopes from tetanus toxin. Eur. J. Immunol.,  1990, 20(3), 477-483.
[http://dx.doi.org/10.1002/eji.1830200304] [PMID:  1690656] 
[38] 
Kaumaya, P.T.; Kobs-Conrad, S.; Seo, Y.H.; Lee, H.; VanBuskirk, A.M.; Feng, N.; Sheridan, J.F.; Stevens, V. Peptide vaccines incorporating a ‘promiscuous’ T-cell epitope bypass certain haplotype restricted immune responses and provide broad spectrum immunogenicity. J. Mol. Recognit.,  1993, 6(2), 81-94.
[http://dx.doi.org/10.1002/jmr.300060206] [PMID:  7508238] 
[39] 
Brigati, J.R.; Petrenko, V.A. Thermostability of landscape phage probes. Anal. Bioanal. Chem.,  2005, 382(6), 1346-1350.
[http://dx.doi.org/10.1007/s00216-005-3289-y] [PMID:  15965686] 
[40] 
Kleinschmidt, W.J.; Douthart, R.J.; Murphy, E.B. Interferon production by T4 coliphage. Nature,  1970, 228(5266), 27-30.
[http://dx.doi.org/10.1038/228027a0] [PMID:  4318493] 
[41] 
Clark, J.R.; March, J.B. Bacteriophages and biotechnology: Vaccines, gene therapy and antibacterials. Trends Biotechnol.,  2006, 24(5), 212-218.
[http://dx.doi.org/10.1016/j.tibtech.2006.03.003] [PMID:  16567009] 
[42] 
Toussi, D.N.; Massari, P. Immune adjuvant effect of molecularly-defined toll-like receptor ligands. Vaccines (Basel),  2014, 2(2), 323-353.
[http://dx.doi.org/10.3390/vaccines2020323] [PMID:  26344622] 
[43] 
Awasthi, S. Toll-like receptor-4 modulation for cancer immunotherapy. Front. Immunol.,  2014, 5, 328.
[http://dx.doi.org/10.3389/fimmu.2014.00328] [PMID:  25120541] 
[44] 
Agrawal, S.; Kandimalla, E.R. modulation of toll-like receptor 9 responses through synthetic immunostimulatory motifs of DNA. Ann. N. Y. Acad. Sci.,  2003, 1002(1), 30-42.
[http://dx.doi.org/10.1196/annals.1281.005] [PMID:  14751820] 
[45] 
Gamage, L.N.; Ellis, J.; Hayes, S. Immunogenicity of bacteriophage lambda particles displaying porcine Circovirus 2 (PCV2) capsid protein epitopes. Vaccine,  2009, 27(47), 6595-6604.
[http://dx.doi.org/10.1016/j.vaccine.2009.08.019] [PMID:  19712770] 
[46] 
Lu, D.; Jimenez, X.; Zhang, H.; Bohlen, P.; Witte, L.; Zhu, Z. Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. Int. J. Cancer,  2002, 97(3), 393-399.
[http://dx.doi.org/10.1002/ijc.1634] [PMID:  11774295] 
[47] 
Conrad, U.; Scheller, J. Considerations on antibody-phage display methodology. Comb. Chem. High Throughput Screen.,  2005, 8(2), 117-126.
[http://dx.doi.org/10.2174/1386207053258532] [PMID:  15777175] 
[48] 
Carter, P.J. Potent antibody therapeutics by design. Nat. Rev. Immunol.,  2006, 6(5), 343-357.
[http://dx.doi.org/10.1038/nri1837] [PMID:  16622479] 
[49] 
Neves, H.; Kwok, H.F. Recent advances in the field of anti-cancer immunotherapy. BBA Clin.,  2015, 3, 280-288.
[http://dx.doi.org/10.1016/j.bbacli.2015.04.001] [PMID:  26673349] 
[50] 
Baselga, J.; Tripathy, D.; Mendelsohn, J.; Baughman, S.; Benz, C.C.; Dantis, L.; Sklarin, N.T.; Seidman, A.D.; Hudis, C.A.; Moore, J.; Rosen, P.P.; Twaddell, T.; Henderson, I.C.; Norton, L. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J. Clin. Oncol.,  1996, 14(3), 737-744.
[http://dx.doi.org/10.1200/JCO.1996.14.3.737] [PMID:  8622019] 
[51] 
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. N. Engl. J. Med.,  2004, 351(4), 337-345.
[http://dx.doi.org/10.1056/NEJMoa033025] [PMID:  15269313] 
[52] 
Zhou, Y.; Zou, H.; Zhang, S.; Marks, J.D. Internalizing cancer antibodies from phage libraries selected on tumor cells and yeast-displayed tumor antigens. J. Mol. Biol.,  2010, 404(1), 88-99.
[http://dx.doi.org/10.1016/j.jmb.2010.09.006] [PMID:  20851130] 
[53] 
Clackson, T.; Hoogenboom, H.R.; Griffiths, A.D.; Winter, G. Making antibody fragments using phage display libraries. Nature,  1991, 352(6336), 624-628.
[http://dx.doi.org/10.1038/352624a0] [PMID:  1907718] 
[54] 
Krag, D.N.; Shukla, G.S.; Shen, G-P.; Pero, S.; Ashikaga, T.; Fuller, S.; Weaver, D.L.; Burdette-Radoux, S.; Thomas, C. Selection of tumor-binding ligands in cancer patients with phage display libraries. Cancer Res.,  2006, 66(15), 7724-7733.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4441] [PMID:  16885375] 
[55] 
Salvatore, G.; Beers, R.; Margulies, I.; Kreitman, R.J.; Pastan, I. Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display. Clin. Cancer Res.,  2002, 8(4), 995-1002.
[PMID:  11948105] 
[56] 
Neefjes, J.; Jongsma, M.L.; Paul, P.; Bakke, O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat. Rev. Immunol.,  2011, 11(12), 823-836.
[http://dx.doi.org/10.1038/nri3084] [PMID:  22076556] 
[57] 
Richman, S.A.; Kranz, D.M. Display, engineering, and applications of antigen-specific T cell receptors. Biomol. Eng.,  2007, 24(4), 361-373.
[http://dx.doi.org/10.1016/j.bioeng.2007.02.009] [PMID:  17409021] 
[58] 
Spear, T.T.; Nagato, K.; Nishimura, M.I. Strategies to genetically engineer T cells for cancer immunotherapy. Cancer Immunol. Immunother.,  2016, 65(6), 631-649.
[http://dx.doi.org/10.1007/s00262-016-1842-5] [PMID:  27138532] 
[59] 
Zhao, Y.; Bennett, A.D.; Zheng, Z.; Wang, Q.J.; Robbins, P.F.; Yu, L.Y.; Li, Y.; Molloy, P.E.; Dunn, S.M.; Jakobsen, B.K.; Rosenberg, S.A.; Morgan, R.A. High-affinity TCRs generated by phage display provide CD4+ T cells with the ability to recognize and kill tumor cell lines. J. Immunol.,  2007, 179(9), 5845-5854.
[http://dx.doi.org/10.4049/jimmunol.179.9.5845] [PMID:  17947658] 
[60] 
Holler, P.D.; Holman, P.O.; Shusta, E.V.; O’Herrin, S.; Wittrup, K.D.; Kranz, D.M. In vitro evolution of a T cell receptor with high affinity for peptide/MHC. Proc. Natl. Acad. Sci. USA,  2000, 97(10), 5387-5392.
[http://dx.doi.org/10.1073/pnas.080078297] [PMID:  10779548] 
[61] 
Hosseinzadeh, F.; Mohammadi, S.; Nejatollahi, F. production and evaluation of specific single-chain antibodies against CTLA-4 for cancer-targeted therapy. Rep. Biochem. Mol. Biol.,  2017, 6(1), 8-14.
[PMID:  29090224] 
[62] 
Aghebati-Maleki, L.; Younesi, V.; Jadidi-Niaragh, F.; Baradaran, B.; Majidi, J.; Yousefi, M. Isolation and characterization of anti ROR1 single chain fragment variable antibodies using phage display technique. Hum. Antibodies,  2017, 25(1-2), 57-63.
[http://dx.doi.org/10.3233/HAB-170310] [PMID:  28128766] 
[63] 
Asadi-Ghalehni, M.; Ghaemmaghami, M.; Klimka, A.; Javanmardi, M.; Navari, M.; Rasaee, M.J. Cancer immunotherapy by a recombinant phage vaccine displaying EGFR mimotope: An in vivo study. Immunopharmacol. Immunotoxicol.,  2015, 37(3), 274-279.
[http://dx.doi.org/10.3109/08923973.2015.1027917] [PMID:  25990849] 
[64] 
Zhikui, L.; Changcun, G.; Yongzhan, N.; Fengtian, H.; Xingling, R.; Shujun, L.; Zheyi, H.; Ying, H.; Xin, W.; Daiming, F. Screening and identification of recombinant anti-idiotype antibodies against gastric cancer and colon cancer monoclonal antibodies by a phage-displayed single-chain variable fragment library. J. Biomol. Screen.,  2010, 15(3), 308-313.
[http://dx.doi.org/10.1177/1087057109360252] [PMID:  20150588] 
[65] 
Huang, Y-J.; Chen, I.C.; Yu, C-M.; Lee, Y-C.; Hsu, H-J.; Ching, A.T.C.; Chang, H-J.; Yang, A-S. Engineering anti-vascular endothelial growth factor single chain disulfide-stabilized antibody variable fragments (sc-dsFv) with phage-displayed sc-dsFv libraries. J. Biol. Chem.,  2010, 285(11), 7880-7891.
[http://dx.doi.org/10.1074/jbc.M109.061457] [PMID:  20068035] 
[66] 
Shadidi, M.; Sørensen, D.; Dybwad, A.; Furset, G.; Sioud, M. Mucosal vaccination with phage-displayed tumour antigens identified through proteomics-based strategy inhibits the growth and metastasis of 4T1 breast adenocarcinoma. Int. J. Oncol.,  2008, 32(1), 241-247.
[http://dx.doi.org/10.3892/ijo.32.1.241] [PMID:  18097564] 
[67] 
Pameijer, C.R.; Navanjo, A.; Meechoovet, B.; Wagner, J.R.; Aguilar, B.; Wright, C.L.; Chang, W.C.; Brown, C.E.; Jensen, M.C. Conversion of a tumor-binding peptide identified by phage display to a functional chimeric T cell antigen receptor. Cancer Gene Ther.,  2007, 14(1), 91-97.
[http://dx.doi.org/10.1038/sj.cgt.7700993] [PMID:  17024231] 
[68] 
Hardy, B.; Raiter, A. A mimotope peptide-based anti-cancer vaccine selected by BAT monoclonal antibody. Vaccine,  2005, 23(34), 4283-4291.
[http://dx.doi.org/10.1016/j.vaccine.2005.04.009] [PMID:  1591913] 
[69] 
Riemer, A.B.; Hantusch, B.; Sponer, B.; Kraml, G.; Hafner, C.; Zielinski, C.C.; Scheiner, O.; Pehamberger, H.; Jensen-Jarolim, E. High-molecular-weight melanoma-associated antigen mimotope immunizations induce antibodies recognizing melanoma cells. Cancer Immunol. Immunother.,  2005, 54(7), 677-684.
[http://dx.doi.org/10.1007/s00262-004-0632-7] [PMID:  15565329] 
[70] 
Liu, B.; Conrad, F.; Cooperberg, M.R.; Kirpotin, D.B.; Marks, J.D. Mapping tumor epitope space by direct selection of single-chain Fv antibody libraries on prostate cancer cells. Cancer Res.,  2004, 64(2), 704-710.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-2732] [PMID:  14744788] 
[71] 
Riemer, A.B.; Klinger, M.; Wagner, S.; Bernhaus, A.; Mazzucchelli, L.; Pehamberger, H.; Scheiner, O.; Zielinski, C.C.; Jensen-Jarolim, E. Generation of Peptide mimics of the epitope recognized by trastuzumab on the oncogenic protein Her-2/neu. J. Immunol.,  2004, 173(1), 394-401.
[http://dx.doi.org/10.4049/jimmunol.173.1.394] [PMID:  15210798] 
[72] 
Wu, Y.; Wan, Y.; Bian, J.; Zhao, J.; Jia, Z.; Zhou, L.; Zhou, W.; Tan, Y. Phage display particles expressing tumor-specific antigens induce preventive and therapeutic anti-tumor immunity in murine p815 model. Int. J. Cancer,  2002, 98(5), 748-753.
[http://dx.doi.org/10.1002/ijc.10260] [PMID:  11920646] 
[73] 
Coomber, D.W.; Ward, R.L. Isolation of human antibodies against the central DNA binding domain of p53 from an individual with colorectal cancer using antibody phage display. Clin. Cancer Res.,  2001, 7(9), 2802-2808.
[PMID:  11555596] 
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