Abstract
Background: Phage display is an effective technology for generation and selection targeting protein for a variety of purpose, which is based on a direct linkage between the displayed protein and the DNA sequence encoding it and utilized in selecting peptides, improving peptides affinity and indicating protein-protein interactions. Phage particles displaying peptide have the potential to apply in the identification of cell-specific targeting molecules, identification of cancer cell surface biomarkers, identification anti-cancer peptide, and the design of peptide-based anticancer therapy.
Method/Results: Literature searches, reviews and assessments about Phage were performed in this review from PubMed and Medline databases.
Conclusion: The phage display technology is an inexpensive method for expressing exogenous peptides, generating unique peptides that bind any given target and investigating protein-protein interactions. Due to the powerful ability to insert exogenous gene and display exogenous peptides on the surface, phages may represent a powerful peptide delivery system that can be utilized to develop rapid, efficient, safe and inexpensive cancer therapy methods.
Keywords: Phage, anti-cancer, cancer, immunotherapy, protein targeting, protein-protein interactions.
Graphical Abstract
[1]
Organization, W.H. Global health observatory data repository.
2011 See http://apps. who. int/ghodata2011.
[2]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[4]
Whitehurst, T.K.; McGivern, J.P.; Kuzma, J.A. Methods and systems
for direct electrical current stimulation as a therapy for cancer
and other neoplastic diseases. US Patent 6,901,296B1 2005.
[6]
Andersen, B.L.; Farrar, W.B.; Golden-Kreutz, D.; Kutz, L.A.; MacCallum, R.; Courtney, M.E.; Glaser, R. Stress and immune responses after surgical treatment for regional breast cancer. J. Natl. Cancer Inst., 1998, 90(1), 30-36.
[7]
Dale, W.B.; Peter, M.H.; Workgroup, S.I.P.G.W. Antimicrobial prophylaxis for surgery: An advisory statement from the National Surgical Infection Prevention Project. Clin. Infect. Dis., 2004, 38(12), 1706-1715.
[8]
Sørensen, L.; Hørby, J.; Friis, E.; Pilsgaard, B.; Jørgensen, T. Smoking as a risk factor for wound healing and infection in breast cancer surgery. Eur. J. Surg. Oncol (EJSO)., 2002, 28(8), 815-820.
[9]
Oliver, R.; Harstrick, A. Combination therapy using anti-egfr antibodies
and anti-hormonal agents. CA Patent 2,449,166A1. 2002.
[10]
Moyad, M. Promoting Wellness Beyond Hormone Therapy: Options for Prostate Cancer Patients; Spry Publishing, 2013.
[11]
Early Breast Cancer Trialists’ Collaborative Group (EBCTC). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet, 2005, 365(9472), 1687-1717.
[13]
Pranjol, M.Z.I.; Hajitou, A. Bacteriophage-derived vectors for targeted cancer gene therapy. Viruses, 2015, 7(1), 268-284.
[14]
Mellman, I.; Coukos, G.; Dranoff, G. Cancer immunotherapy comes of age. Nature, 2011, 480(7378), 480-489.
[15]
Palucka, K.; Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer, 2012, 12(4), 265-277.
[16]
Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12(4), 252-264.
[17]
Candeias, S.M.; Gaipl, U.S. The immune system in cancer prevention, development and therapy. Anti-Canc. Agents Med. Chem., 2016, 16(1), 101-107.
[18]
Mintz, P.J.; Kim, J.; Do, K-A.; Wang, X.; Zinner, R.G.; Cristofanilli, M.; Arap, M.A.; Hong, W.K.; Troncoso, P.; Logothetis, C.J. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat. Biotechnol., 2003, 21(1), 57-63.
[19]
Kalscheuer, S.; Panyam, J. Phage display derived antibodies for the detection of mesenchymal CTCs in TNBC. Cancer Res., 2015, 75(15)(Suppl.), 368-368.
[20]
Smith, T.L.; Yuan, Z.; Cardó-Vila, M.; Claros, C.S.; Adem, A.; Cui, M-H.; Branch, C.A.; Gelovani, J.G.; Libutti, S.K.; Sidman, R.L. AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas. Proc. Natl. Acad. Sci., 2016, 113(9), 2466-2471.
[21]
Hosoya, H.; Dobroff, A.S.; Driessen, W.H.; Cristini, V.; Brinker, L.M.; Staquicini, F.I.; Cardó-Vila, M.; D’Angelo, S.; Ferrara, F.; Proneth, B. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release. Proc. Natl. Acad. Sci., 2016, 113(7), 1877-1882.
[22]
Food and Drug Administration. FDA approval of Listeria-specific bacteriophage preparation on ready-to-eat (RTE) meat and poultry products. 2006.
[23]
Zhao, N.; Qin, Y.; Liu, H.; Cheng, Z. Tumor-targeting peptides: Ligands for molecular imaging and therapy. Anti-Canc. Agents Med. Chem., 2018, 18(1), 74-86.
[24]
Smith, G.P. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science, 1985, 228(4705), 1315-1317.
[25]
Lindqvist, B.H.; Naderi, S. Peptide presentation by bacteriophage P4. FEMS Microbiol. Rev., 1995, 17(1-2), 33-39.
[26]
Ren, Z.; Black, L.; Lewis, G.; Wingfield, P.; Locke, E.; Steven, A. Phage display of intact domains at high copy number: a system based on SOC, the small outer capsid protein of bacteriophage T4. Protein Sci., 1996, 5(9), 1833-1843.
[27]
Danner, S.; Belasco, J.G. T7 phage display: A novel genetic selection system for cloning RNA-binding proteins from cDNA libraries. Proc. Natl. Acad. Sci. USA, 2001, 98(23), 12954-12959.
[28]
Rosenberg, A.; Griffin, K.; Studier, F.W.; McCormick, M.; Berg, J.; Novy, R.; Mierendorf, R. T7Select phage display system: A powerful new protein display system based on bacteriophage T7. Innovations, 1996, 6, 1-6.
[30]
Marvin, D.; Hale, R.; Nave, C.; Citterich, M.H. Molecular models and structural comparisons of native and mutant class I filamentous bacteriophages: Ff (fd, f1, M13), If1 and IKe. J. Mol. Biol., 1994, 235(1), 260-286.
[31]
Fuh, G.; Sidhu, S.S. Efficient phage display of polypeptides fused to the carboxy‐terminus of the M13 gene‐3 minor coat protein. FEBS Lett., 2000, 480(2-3), 231-234.
[32]
Weiss, G.A.; Roth, T.A.; Baldi, P.F.; Sidhu, S.S. Comprehensive mutagenesis of the C-terminal domain of the M13 gene-3 minor coat protein: The requirements for assembly into the bacteriophage particle. J. Mol. Biol., 2003, 332(4), 777-782.
[33]
Liao, W.; Hong, L.; Wei, F.; Zhu, S-G.; Zhao, X-S. Improving
phage antibody chip by pVIII display system. Acta Phys. Chim.
Sin, 2005, 21(05), 508-511.
[34]
Liu, P.; Han, L.; Wang, F.; Petrenko, V.A.; Liu, A. Gold nanoprobe functionalized with specific fusion protein selection from phage display and its application in rapid, selective and sensitive colorimetric biosensing of Staphylococcus aureus. Biosens. Bioelectron., 2016, 82, 195-203.
[36]
Yan, W.; Qunying, L.; Rongkai, G. Construction of ScFv expression
vectors and expression of anti HBs ScFv Ch. J. Microbiol.
Immunol., 1997, 01
[37]
Qi, C.; Lin, Y.; Feng, J.; Wang, Z-H.; Zhu, C-F.; Meng, Y-H.; Yan, X-Y.; Wan, L-J.; Jin, G. Phage M13KO7 detection with biosensor based on imaging ellipsometry and AFM microscopic confirmation. Virus Res., 2009, 140(1), 79-84.
[38]
Wu, X.; Yan, Q.; Huang, Y.; Huang, H.; Su, Z.; Xiao, J.; Zeng, Y.; Wang, Y.; Nie, C.; Yang, Y. Isolation of a novel basic FGF‐binding peptide with potent antiangiogenetic activity. J. Cell. Mol. Med., 2010, 14(1‐2), 351-356.
[39]
Yacoby, I.; Shamis, M.; Bar, H.; Shabat, D.; Benhar, I. Targeting antibacterial agents by using drug-carrying filamentous bacteriophages. Antimicrob. Agents Chemother., 2006, 50(6), 2087-2097.
[40]
Cao, B.; Yang, M.; Mao, C. Phage as a genetically modifiable supramacromolecule in chemistry, materials and medicine. Acc. Chem. Res., 2016, 49(6), 1111-1120.
[41]
Frenkel, D.; Katz, O.; Solomon, B. Immunization against Alzheimer’s β-amyloid plaques via EFRH phage administration. Proc. Natl. Acad. Sci. USA, 2000, 97(21), 11455-11459.
[42]
Molek, P.; Strukelj, B.; Bratkovic, T. Peptide phage display as a tool for drug discovery: Targeting membrane receptors. Molecules, 2011, 16(1), 857-887.
[43]
Barry, M.A.; Dower, W.J.; Johnston, S.A. Toward cell–targeting gene therapy vectors: Selection of cell–binding peptides from random peptide–presenting phage libraries. Nat. Med., 1996, 2(3), 299-305.
[44]
Chester, K.A.; Begent, R.; Robson, L.; Keep, P.; Pedley, R. LIBiol, J.B.; Boxer, G.; Green, A.; Winter, G.; Cochet, O. Phage libraries for generation of clinically useful antibodies. Lancet, 1994, 343(8895), 455-456.
[45]
Hanes, J.; Schaffitzel, C.; Knappik, A.; Plückthun, A. Picomolar affinity antibodies from a fully synthetic naive library selected and evolved by ribosome display. Nat. Biotechnol., 2000, 18(12), 1287-1292.
[46]
Hoogenboom, H.R. Selecting and screening recombinant antibody libraries. Nat. Biotechnol., 2005, 23(9), 1105-1116.
[47]
Prisco, A.; De Berardinis, P. Filamentous bacteriophage fd as an antigen delivery system in vaccination. Int. J. Mol. Sci., 2012, 13(4), 5179-5194.
[48]
van Houten, N.E.; Henry, K.A.; Smith, G.P.; Scott, J.K. Engineering filamentous phage carriers to improve focusing of antibody responses against peptides. Vaccine, 2010, 28(10), 2174-2185.
[49]
Górski, A.; Ważna, E.; Dąbrowska, B-W.; Dąbrowska, K.; Świtała-Jeleń, K.; Międzybrodzki, R. Bacteriophage translocation. FEMS Immunol. Med. Microbiol., 2006, 46(3), 313-319.
[50]
Pajtasz-Piasecka, E.; Rossowska, J.; Duś, D.; Weber-Dąbrowska, B.; Zabłocka, A.; Górski, A. Bacteriophages support anti-tumor response initiated by DC-based vaccine against murine transplantable colon carcinoma. Immunol. Lett., 2008, 116(1), 24-32.
[51]
Sartorius, R.; Pisu, P.; D’Apice, L.; Pizzella, L.; Romano, C.; Cortese, G.; Giorgini, A.; Santoni, A.; Velotti, F.; De Berardinis, P. The use of filamentous bacteriophage fd to deliver MAGE-A10 or MAGE-A3 HLA-A2-restricted peptides and to induce strong antitumor CTL responses. J. Immunol., 2008, 180(6), 3719-3728.
[52]
Tong, A.H.Y.; Drees, B.; Nardelli, G.; Bader, G.D.; Brannetti, B.; Castagnoli, L.; Evangelista, M.; Ferracuti, S.; Nelson, B.; Paoluzi, S. A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules. Science, 2002, 295(5553), 321-324.
[53]
Li, Y.; Moysey, R.; Molloy, P.E.; Vuidepot, A-L.; Mahon, T.; Baston, E.; Dunn, S.; Liddy, N.; Jacob, J.; Jakobsen, B.K. Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nat. Biotechnol., 2005, 23(3), 349-354.
[54]
Deutscher, S.L. Phage display in molecular imaging and diagnosis of cancer. Chem. Rev., 2010, 110(5), 3196-3211.
[55]
Clark, J.R.; March, J.B. Bacteriophages and biotechnology: Vaccines, gene therapy and antibacterials. Trends Biotechnol., 2006, 24(5), 212-218.
[56]
Lauterbach, S.B.; Lanzillotti, R.; Coetzer, T.L. Construction and use of Plasmodium falciparum phage display libraries to identify host parasite interactions. Malar. J., 2003, 2(1), 47.
[57]
Brown, K.C. New approaches for cell-specific targeting: identification of cell-selective peptides from combinatorial libraries. Curr. Opin. Chem. Biol., 2000, 4(1), 16-21.
[58]
Shadidi, M.; Sioud, M. Identification of novel carrier peptides for the specific delivery of therapeutics into cancer cells. FASEB J., 2003, 17(2), 256-258.
[59]
Zhang, J.; Spring, H.; Schwab, M. Neuroblastoma tumor cell-binding peptides identified through random peptide phage display. Cancer Lett., 2001, 171(2), 153-164.
[60]
Fagbohun, O.A.; Bedi, D.; Grabchenko, N.I.; Deinnocentes, P.A.; Bird, R.C.; Petrenko, V.A. Landscape phages and their fusion proteins targeted to breast cancer cells. Protein Eng. Des. Sel., 2012, 25(6), 271-283.
[61]
Pasqualini, R.; Ruoslahti, E. Organ targeting in vivo using phage display peptide libraries. Nature, 1996, 380(6572), 364-366.
[62]
Li, X.; Mao, C. Using phage as a platform to select cancer cell-targeting peptides. Virus Hybrids Nanomater; Methods Protocols, 2014, pp. 57-68.
[63]
Park, H-Y.; Lee, K-J.; Lee, S-J.; Yoon, M-Y. Screening of peptides bound to breast cancer stem cell specific surface marker CD44 by phage display. Mol. Biotechnol., 2012, 51(3), 212-220.
[64]
Feng, M.; Gao, W.; Wang, R.; Chen, W.; Man, Y-G.; Figg, W.D.; Wang, X.W.; Dimitrov, D.S.; Ho, M. Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma. Proc. Natl. Acad. Sci., 2013, 110(12), E1083-E1091.
[65]
Perea, S.E.; Reyes, O.; Puchades, Y.; Mendoza, O.; Vispo, N.S.; Torrens, I.; Santos, A.; Silva, R.; Acevedo, B.; López, E. Antitumor effect of a novel proapoptotic peptide that impairs the phosphorylation by the protein kinase 2 (casein kinase 2). Cancer Res., 2004, 64(19), 7127-7129.
[66]
Abbineni, G.; Modali, S.; Safiejko-Mroczka, B.; Petrenko, V.A.; Mao, C. Evolutionary selection of new breast cancer cell-targeting peptides and phages with the cell-targeting peptides fully displayed on the major coat and their effects on actin dynamics during cell internalization. Mol. Pharm., 2010, 7(5), 1629-1642.
[67]
Matsuo, A.L.; Tanaka, A.S.; Juliano, M.A.; Rodrigues, E.G.; Travassos, L.R. A novel melanoma-targeting peptide screened by phage display exhibits antitumor activity. J. Mol. Med., 2010, 88(12), 1255-1264.
[68]
Zhou, C.; Kang, J.; Wang, X.; Wei, W.; Jiang, W. Phage display screening identifies a novel peptide to suppress ovarian cancer cells in vitro and in vivo in mouse models. BMC Cancer, 2015, 15(1), 1.
[69]
Shukla, G.S.; Krag, D.N.; Peletskaya, E.N.; Pero, S.C.; Sun, Y-J.; Carman, C.L.; McCahill, L.E.; Roland, T.A. Intravenous infusion of phage-displayed antibody library in human cancer patients: enrichment and cancer-specificity of tumor-homing phage-antibodies. Cancer Immunol. Immunother., 2013, 62(8), 1397-1410.
[70]
Zhang, L.; Giraudo, E.; Hoffman, J.A.; Hanahan, D.; Ruoslahti, E. Lymphatic zip codes in premalignant lesions and tumors. Cancer Res., 2006, 66(11), 5696-5706.
[71]
Larsen, S.A.; Meldgaard, T.; Fridriksdottir, A.J.R.; Lykkemark, S.; Poulsen, P.C.; Overgaard, L.F.; Petersen, H.B.; Petersen, O.W.; Kristensen, P. Raising an antibody specific to breast cancer subpopulations using phage display on tissue sections. Cancer Genomics Proteomics, 2016, 13(1), 21-30.
[72]
Kuhn, P.; Fühner, V.; Unkauf, T.; Moreira, G.M.S.G.; Frenzel, A.; Miethe, S.; Hust, M. Recombinant antibodies for diagnostics and therapy against pathogens and toxins generated by phage display. Proteomics Clin. Appl., 2016, 10(9-10), 922-948.
[73]
Mössner, E.; Hofer, T.U.; Hosse, R.J.; Umaña, P. Antibodies to carcinoembryonic antigen (CEA), methods of making same, and uses thereof. US Patent 20,160,075,795 2015.
[74]
Koivunen, E.; Arap, W.; Valtanen, H.; Rainisalo, A.; Medina, O.P.; Heikkilä, P.; Kantor, C.; Gahmberg, C.G.; Salo, T.; Konttinen, Y.T. Tumor targeting with a selective gelatinase inhibitor. Nat. Biotechnol., 1999, 17(8), 768-774.
[75]
Robbins, S.M.; Rahn, J.; Senger, D.L. Brain tumor targeting peptides and methods. EP Patent 2,714,090. 2015.
[76]
Lee, K.J.; Lee, J.H.; Chung, H.K.; Choi, J.; Park, J.; Park, S.S.; Ju, E.J.; Park, J.; Shin, S.H.; Park, H.J. Novel peptides functionally targeting in vivo human lung cancer discovered by in vivo peptide displayed phage screening. Amino Acids, 2015, 47(2), 281-289.
[77]
Newton, J.R.; Kelly, K.A.; Mahmood, U.; Weissleder, R.; Deutscher, S.L. In vivo selection of phage for the optical imaging of PC-3 human prostate carcinoma in mice. Neoplasia, 2006, 8(9), 772-780.
[78]
Matsuo, A.L.; Juliano, M.A.; Figueiredo, C.R.; Batista, W.L.; Tanaka, A.S.; Travassos, L.R. A new phage-display tumor-homing peptide fused to antiangiogenic peptide generates a novel bioactive molecule with antimelanoma activity. Mol. Cancer Res., 2011, 9(11), 1471-1478.
[79]
Huls, G.A.; Heijnen, I.A.; Cuomo, M.E.; Koningsberger, J.C.; Wiegman, L.; Boel, E.; Loyson, S.A.; Helfrich, W.; van Berge Henegouwen, G.P.; van Meijer, M. A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments. Nat. Biotechnol., 1999, 17(3), 276-281.
[80]
Lai, Y-D.; Wu, Y-Y.; Tsai, Y-J.; Tsai, Y-S.; Lin, Y-Y.; Lai, S-L.; Huang, C-Y.; Lok, Y-Y.; Hu, C-Y.; Lai, J-S. Generation of potent anti-vascular endothelial growth factor neutralizing antibodies from mouse phage display library for cancer therapy. Int. J. Mol. Sci., 2016, 17(2), 214.
[81]
Dabrowska, K.; Kazmierczak, Z.; Majewska, J.; Miernikiewicz, P.; Piotrowicz, A.; Wietrzyk, J.; Lecion, D.; Hodyra, K.; Nasulewicz-Goldeman, A.; Owczarek, B. Bacteriophages displaying anticancer peptides in combined antibacterial and anticancer treatment. Future Microbiol., 2014, 9(7), 861-869.
[82]
Ghosh, D.; Kohli, A.G.; Moser, F.; Endy, D.; Belcher, A.M. Refactored M13 bacteriophage as a platform for tumor cell imaging and drug delivery. ACS Synth. Biol., 2012, 1(12), 576-582.
[83]
Gandra, N.; Abbineni, G.; Qu, X.; Huai, Y.; Wang, L.; Mao, C. Bacteriophage bionanowire as a carrier for both cancer‐targeting peptides and photosensitizers and its use in selective cancer cell killing by photodynamic therapy. Small, 2013, 9(2), 215-221.
[84]
Wang, Y.; Su, Q.; Dong, S.; Shi, H.; Gao, X.; Wang, L. Hybrid phage displaying SLAQVKYTSASSI induces protection against Candida albicans challenge in BALB/c mice. Human Vacc. Immunotherapeut., 2014, 10(4), 1057-1063.
[85]
Del Pozzo, G.; Mascolo, D.; Sartorius, R.; Citro, A.; Barba, P.; D'Apice, L.; De Berardinis, P. Triggering DTH and CTL activity by fd filamentous bacteriophages: Role of CD4+ T Cells in Memory Responses. J. Biomed. Biotechonl., 2010, 2010, 894971. 2010.
[86]
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.
[87]
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.
[88]
Zhou, F.; Teng, F.; Deng, P.; Meng, N.; Song, Z.; Feng, R. Recent progress of nano-drug delivery system for liver cancer treatment. Anti-Canc. Agents Med. Chem., 2017, 17, 1884-1897. 2017.
[89]
Sartorius, R.; Bettua, C.; D’Apice, L.; Caivano, A.; Trovato, M.; Russo, D.; Zanoni, I.; Granucci, F.; Mascolo, D.; Barba, P. Vaccination with filamentous bacteriophages targeting DEC‐205 induces DC maturation and potent anti‐tumor T‐cell responses in the absence of adjuvants. Eur. J. Immunol., 2011, 41(9), 2573-2584.
[90]
Romano, G.; Pacilio, C.; Giordano, A. Gene transfer technology in therapy: current applications and future goals. Stem Cells, 1999, 17(4), 191-202.
[91]
Larocca, D.; Witte, A.; Johnson, W.; Pierce, G.F.; Baird, A. Targeting bacteriophage to mammalian cell surface receptors for gene delivery. Hum. Gene Ther., 1998, 9(16), 2393-2399.
[92]
Kia, A.; Przystal, J.M.; Nianiaris, N.; Mazarakis, N.D.; Mintz, P.J.; Hajitou, A. Dual systemic tumor targeting with ligand-directed phage and Grp78 promoter induces tumor regression. Mol. Canc. Therapeut., 2012, 11(12), 2566-2577.
[93]
Hajitou, A.; Rangel, R.; Trepel, M.; Soghomonyan, S.; Gelovani, J.G.; Alauddin, M.M.; Pasqualini, R.; Arap, W. Design and construction of targeted AAVP vectors for mammalian cell transduction. Nat. Protoc., 2007, 2(3), 523-531.
[94]
Cao, B.; Yang, M.; Mao, C. Phage as a Genetically Modifiable
Supramacromolecule in Chemistry, Materials and Medicine. ACC.
Chem. Res., 2016, 21, 49-54.
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