Abstract
The adaptive immune response against cancer consists of two arms: the humoral response from B cells, and the cell-mediated response from T cells. The humoral response has the advantage of diversity, theoretically recognizing antigens of any type (sugar, protein, lipid, etc.), but is generally limited to surface-expressed targets. T cells on the other hand, can recognize intracellular targets, but only if they are proteins, and presented as small peptide fragments on major histocompatibility complex (MHC) cell surface antigens. However, with advances in protein engineering and phage display, it has become feasible to quickly identify and generate antibodies or single-chain variable fragments against peptide-MHC, thus bridging the two arms, and allowing for recognition, identification, and effector responses against cells expressing intracellular targets.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Smith GP (1985) Filamentous fusion phage - novel expression vectors that display cloned antigens on the virion surface. Science 228(4705):1315–1317. doi:10.1126/Science.4001944
Choo Y, Klug A (1994) Toward a code for the interactions of zinc fingers with DNA: selection of randomized fingers displayed on phage. Proc Natl Acad Sci U S A 91(23):11163–11167
Cwirla SE, Peters EA, Barrett RW, Dower WJ (1990) Peptides on phage: a vast library of peptides for identifying ligands. Proc Natl Acad Sci U S A 87(16):6378–6382
Devlin JJ, Panganiban LC, Devlin PE (1990) Random peptide libraries: a source of specific protein binding molecules. Science 249(4967):404–406
Jamieson AC, Kim SH, Wells JA (1994) In vitro selection of zinc fingers with altered DNA-binding specificity. Biochemistry 33(19):5689–5695
Lowman HB, Bass SH, Simpson N, Wells JA (1991) Selecting high-affinity binding proteins by monovalent phage display. Biochemistry 30(45):10832–10838
Rebar EJ, Pabo CO (1994) Zinc finger phage: affinity selection of fingers with new DNA-binding specificities. Science 263(5147):671–673
Scott JK, Smith GP (1990) Searching for peptide ligands with an epitope library. Science 249(4967):386–390
Wang CI, Yang Q, Craik CS (1995) Isolation of a high affinity inhibitor of urokinase-type plasminogen activator by phage display of ecotin. J Biol Chem 270(20):12250–12256
Barbas CF 3rd (1995) Synthetic human antibodies. Nat Med 1(8):837–839
Chames P, Hufton SE, Coulie PG, Uchanska-Ziegler B, Hoogenboom HR (2000) Direct selection of a human antibody fragment directed against the tumor T-cell epitope HLA-A1-MAGE-A1 from a nonimmunized phage-Fab library. Proc Natl Acad Sci U S A 97(14):7969–7974
Dao T, Yan S, Veomett N, Pankov D, Zhou L, Korontsvit T, Scott A, Whitten J, Maslak P, Casey E, Tan T, Liu H, Zakhaleva V, Curcio M, Doubrovina E, O’Reilly RJ, Liu C, Scheinberg DA (2013) Targeting the intracellular WT1 oncogene product with a therapeutic human antibody. Sci Transl Med 5(176):176ra133. doi:10.1126/scitranslmed.3005661
Mao S, Gao C, Lo CH, Wirsching P, Wong CH, Janda KD (1999) Phage-display library selection of high-affinity human single-chain antibodies to tumor-associated carbohydrate antigens sialyl Lewisx and Lewisx. Proc Natl Acad Sci U S A 96(12):6953–6958
Nelson AL, Dhimolea E, Reichert JM (2010) Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 9(10):767–774. doi:10.1038/nrd3229
Rauchenberger R, Borges E, Thomassen-Wolf E, Rom E, Adar R, Yaniv Y, Malka M, Chumakov I, Kotzer S, Resnitzky D, Knappik A, Reiffert S, Prassler J, Jury K, Waldherr D, Bauer S, Kretzschmar T, Yayon A, Rothe C (2003) Human combinatorial Fab library yielding specific and functional antibodies against the human fibroblast growth factor receptor 3. J Biol Chem 278(40):38194–38205. doi:10.1074/jbc.M303164200
Saggy I, Wine Y, Shefet-Carasso L, Nahary L, Georgiou G, Benhar I (2012) Antibody isolation from immunized animals: comparison of phage display and antibody discovery via V gene repertoire mining. Protein Eng Des Sel 25(10):539–549. doi:10.1093/protein/gzs060
Schoonbroodt S, Steukers M, Viswanathan M, Frans N, Timmermans M, Wehnert A, Nguyen M, Ladner RC, Hoet RM (2008) Engineering antibody heavy chain CDR3 to create a phage display Fab library rich in antibodies that bind charged carbohydrates. J Immunol 181(9):6213–6221
Vaughan TJ, Williams AJ, Pritchard K, Osbourn JK, Pope AR, Earnshaw JC, McCafferty J, Hodits RA, Wilton J, Johnson KS (1996) Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol 14(3):309–314. doi:10.1038/nbt0396-309
Barbas CF 3rd, Kang AS, Lerner RA, Benkovic SJ (1991) Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc Natl Acad Sci U S A 88(18):7978–7982
Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA 3rd, Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6(5):343–345. doi:10.1038/nmeth.1318
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Santich, B.H., Liu, H., Liu, C., Cheung, NK.V. (2015). Generation of TCR-Like Antibodies Using Phage Display. In: Houen, G. (eds) Peptide Antibodies. Methods in Molecular Biology, vol 1348. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2999-3_17
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2999-3_17
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2998-6
Online ISBN: 978-1-4939-2999-3
eBook Packages: Springer Protocols