Intracellular antibodies: A revolution waiting to happen?

Current Opinion in Molecular Therapeutics

Volumn 8, Issue 1, 2006, Pages 17-23

  Stocks, Martin ^a  

^a Iclectus Limited   (United Kingdom)

Author keywords

Drug discovery; Intrabody; Intracellular antibody; Therapeutic; Validation

Indexed keywords

ACTIN BINDING PROTEIN; ALPHA SYNUCLEIN; AMYLOID BETA PROTEIN ANTIBODY; AMYLOID PRECURSOR PROTEIN; ANGIOPOIETIN RECEPTOR; ANKYRIN; BETA GALACTOSIDASE; CELL ANTIBODY; CHAPERONE; CORE PROTEIN; EPSTEIN BARR VIRUS ANTIGEN; HEPATITIS B ANTIBODY; HEPATITIS B VIRUS X PROTEIN; HEPATITIS C ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; HUNTINGTIN; IMMUNOGLOBULIN F(AB) FRAGMENT; LATENCY ASSOCIATED NUCLEAR ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MALTOSE BINDING PROTEIN; NONSTRUCTURAL PROTEIN 3; PROTEIN ANTIBODY; PROTEIN E7; RAS PROTEIN; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; TETRANECTIN; UNINDEXED DRUG; VASCULOTROPIN RECEPTOR; VIF PROTEIN; VIRUS ENVELOPE PROTEIN;

ANTIBODY AFFINITY; ANTIBODY ISOLATION; ANTIBODY LIBRARY; ANTIBODY SCREENING; ANTIBODY SPECIFICITY; ANTIBODY STRUCTURE; BINDING AFFINITY; BIOENGINEERING; DRUG RESEARCH; GENE THERAPY; GOLGI COMPLEX; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUNTINGTON CHOREA; IMMUNOASSAY; IN VIVO STUDY; KAPOSI SARCOMA; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; PLANT VIRUS; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN LOCALIZATION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REVIEW; ROUGH ENDOPLASMIC RETICULUM; VACCINE PRODUCTION; VIRAL GENE DELIVERY SYSTEM;

ANIMALS; ANTIBODIES; BIOTECHNOLOGY; DRUG EVALUATION, PRECLINICAL; HUMANS; INTRACELLULAR SPACE;

HEPATITIS B VIRUS; HEPATITIS C VIRUS; HUMAN HERPESVIRUS 4; HUMAN IMMUNODEFICIENCY VIRUS;

EID: 32544439200     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (81)

1. Antman KH, Livingston DM: Intracellular neutralization of SV40 tumor antigens following microinjection of specific antibody. Cell (1980) 19(3):627-635.
2. H domains. Protein Sci (1999) 8(11):2245-2250.
3. L domain stability. J Mol Biol (1999) 291(6):1119-1128.
4. Werge TM, Biocca S, Cattaneo A: Intracellular immunization. Cloning and intracellular expression of a monoclonal antibody to the p21Ras protein. FEBS Lett (1990) 274(1-2):193-198.
5. Duan L, Bagasra O, Laughlin MA, Oakes JW, Pomerantz RJ: Potent Inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody. Proc Natl Acad Sci USA (1994) 91(11):5075-5079.
6. Curiel DT: Targeted tumor cytotoxicity mediated by intracellular single-chain anti-oncogene antibodies. Adv Pharmacol (1997)40:51-84.
7. Levin R, Mhashilkar AM, Dorfman T, Bukovsky A, Zani C, Bagley J, Hinkula J, Niedrig M, Albert J, Wahren B, Goettlinger HG, Marasco WA: Inhibition of early and late events of the HIV-1 replication cycle by cytoplasmic Fab intrabodies against the matrix protein, p17. Mol Med (1997) 3(2):96-110.
8. Cohen PA, Mani JC, Lane DP: Characterization of a new intrabody directed against the N-terminal region of human p53. Oncogene (1998) 17(19):2445-2456.
9. Marasco WA, Haseltine WA, Chen SY: Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody. Proc Natl Acad Sci USA (1993) 90(16):7889-7893.
10. Beerli RR, Weis W, Hynes NE: Intracellular expression of single chain antibodies reverts ErbB-2 transformation. J Biol Chem (1994) 269(39):23931-23936.
11. Richardson JH, Sodroski JG, Waldmann TA, Marasco WA: Phenotypic knockout of the high-affinity human interleukin 2 receptor by intracellular single-chain antibodies against the α subunit of the receptor. Proc Natl Acad Sci USA (1995) 92(8):3137-3141.
12. Yuan Q, Strauch KL, Lobb RR, Hemler ME: Intracellular single-chain antibody inhibits integrin VLA-4 maturation and function. Biochem J (1996) 318(2):591-596.
13. Cattaneo A, Biocca S: The selection of intracellular antibodies. Trends Biotechnol (1999) 17(3):115-121.
14. Visintin M, Tse E, Axelson H, Rabbitts TH, Cattaneo A: Selection of antibodies for intracellular function using a two-hybrid in vivo system. Proc Natl Acad Sci USA (1999) 96(21):11723-11728.
15. der Maur AA, Zahnd C, Fischer F, Spinelli S, Honegger A, Cambillau C, Escher D, Pluckthun A, Barberis A: Direct in vivo screening of intrabody libraries constructed on a highly stable single-chain framework. J Biol Chem (2002) 277(47):45075-45085.
16. Ewert S, Honegger A, Pluckthun A: Stability improvement of antibodies for extracellular and intracellular applications: CDR grafting to stable frameworks and structure-based framework engineering. Methods (2004) 34(2):184-199.
17. Visintin M, Settanni G, Maritan A, Graziosi S, Marks JD, Cattaneo A: The intracellular antibody capture technology (IACT): Towards a consensus sequence for intracellular antibodies. J Mol Biol (2002) 317(1):73-83.
18. Tse E, Lobato MN, Forster A, Tanaka T, Chung GT, Rabbitts TH: Intracellular antibody capture technology: Application to selection of intracellular antibodies recognising the BCR-ABL oncogenic protein. J Mol Biol (2002) 317(1):85-94.
19. Tanaka T, Rabbitts TH: Intrabodies based on intracellular capture frameworks that bind the Ras protein with high affinity and impair oncogenic transformation. EMBO J (2003) 22(5):1025-1035.
20. Tanaka T, Chung GT, Forster A, Lobato MN, Rabbitts TH: De novo production of diverse intracellular antibody libraries. Nucleic Acids Res (2003) 31(5):e23.
21. Tanaka T, Lobato MN, Rabbitts TH: Single domain intracellular antibodies: A minimal fragment for direct in vivo selection of antigen-specific intrabodies. J Mol Biol {2003) 331(5):1109-1120.
22. Gennari F, Mehta S, Wang Y, St Clair Tallarico A, Palu G, Marasco WA: Direct phage to intrabody screening (DPIS): Demonstration by isolation of cytosolic intrabodies against the TES1 site of Epstein Barr virus latent membrane protein 1 (LMP1) that block NF-κB transactivation. J Mol Biol (2004) 335(1):193-207.
23. L) intracellular antibody specific for the amino terminus of huntingtin via yeast surface display. J Mol Biol (2004) 342(3):901-912.
24. Saerens D, Pellis M, Loris R, Pardon E, Dumoulin M, Matagne A, Wyns L, Muyldermans S, Conrath K: Identification of a universal VHH framework to graft non-canonical antigen-binding loops of camel single-domain antibodies. J Mol Biol (2005) 352(3):597-607.
25. Paz K, Brennan LA, Iacolina M, Doody J, Hadari YR, Zhu Z: Human single-domain neutralizing intrabodies directed against Etk kinase: A novel approach to impair cellular transformation. Mol Cancer Ther (2005) 4(11):1801-1809.
26. H single-domain intrabodies against Vif strongly neutralize HIV-1 infectivity. J Mol Biol (2004) 340(3):525-542.
27. Nuttall SD, Krishnan UV, Doughty L, Pearson K, Ryan MT, Hoogenraad NJ, Hattarki M, Carmichael JA, Irving RA, Hudson PJ: Isolation and characterization of an IgNAR variable domain specific for the human mitochondrial translocase receptor Tom70. Eur J Biochem (2003) 270(17):3543-3554.
28. Strube RW, Chen SY: Enhanced intracellular stability of sFv-Fc fusion intrabodies. Methods (2004) 34(2):179-183.
29. Shaki-Loewenstein S, Zfania R, Hyland S, Wels WS, Benhar I: A universal strategy for stable intracellular antibodies. J Immunol Methods (2005) 303(1-2):19-39.
30. Binz HK, Pluckthun A: Engineered proteins as specific binding reagents. Curr Opin Biotechnol (2005)16(4):459-469.
31. Binz HK, Amstutz P, Pluckthun A: Engineering novel binding proteins from nonimmunoglobulin domains. Nat Biotechnol (2005) 23(10):1257-1268.
32. Hey T, Fiedler E, Rudolph R, Fiedler M: Artificial, non-antibody binding proteins for pharmaceutical and industrial applications. Trends Biotechnol (2005) 23(10):514-522.
33. Miller TW, Messer A: Intrabody applications in neurological disorders: Progress and future prospects. Mol Ther (2005) 12(3):394-401.
34. Visintin M, Meli GA, Cannistraci I, Cattaneo A: Intracellular antibodies for proteomics. J Immunol Methods (2004) 290(1-2):135-153.
35. Lobato MN, Rabbitts TH: Intracellular antibodies as specific reagents for functional ablation: Future therapeutic molecules. Curr Mol Med (2004) 4(5):519-528.
36. Visintin M, Quondam M, Cattaneo A: The intracellular antibody capture technology: Towards the high-throughput selection of functional intracellular antibodies for target validation. Methods (2004) 34(2):200-214.
37. Mhashilkar AM, Biswas DK, LaVecchio J, Pardee AB, Marasco WA: Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-κB antagonists. J Virol (1997) 71(9):6486-6494.
38. Goncalves J, Silva F, Freitas-Vieira A, Santa-Marta M, Malho R, Yang X, Gabuzda D, Barbas C 3rd: Functional neutralization of HIV-1 Vif protein by intracellular immunization inhibits reverse transcription and viral replication. J Biol Chem (2002) 277(35):32036-32045.
39. Corte-Real S, Collins C, Aires da Silva F, Simas JP, Barbas CF 3rd, Chang Y, Moore P, Goncalves J: Intrabodies targeting the Kaposi sarcoma-associated herpesvirus latency antigen inhibit viral persistence in lymphoma cells. Blood (2005) 106(12):3797-3802.
40. Colby DW, Chu Y, Cassady JP, Duennwald M, Zazulak H, Webster JM, Messer A, Lindquist S, Ingram VM, Wittrup KD: Potent inhibition of huntingtin aggregation and cytotoxicity by a disulfide bond-free single-domain intracellular antibody. Proc Natl Acad Sci USA (2004) 101(51):17616-17621.
41. Khoshnan A, Ko J, Patterson PH: Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity. Proc Natl Acad Sci USA (2002) 99(2):1002-1007.
42. Lecert JM, Shirley TL, Zhu Q, Kazantsev A, Amersdorfer P, Housman DE, Messer A, Huston JS: Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington's disease. Proc Natl Acad Sci USA (2001) 98(8):4764-4769.
43. Boonrod K, Galetzka D, Nagy PD, Conrad U, Krczal G: Single-chain antibodies against a plant viral RNA-dependent RNA polymerase confer virus resistance. Nat Biotechnol (2004) 22(7):856-862.
44. Villani ME, Roggero P, Bitti O, Benvenuto E, Franconi R: Immunomodulation of cucumber mosaic virus infection by intrabodies selected in vitro from a stable single-framework phage display library. Plant Mol Biol (2005) 58(3):305-316.
45. Beeril RR, Weis W, Hynes NE: Inhibition of signaling from type 1 receptor tyrosine kinases via intracellular expression of single-chain antibodies. Breast Cancer Res Treat (1996) 38(1):11-17.
46. Jannot CB, Beeril RR, Mason S, Gullick WJ, Hynes NE: Intracellular expression of a single-chain antibody directed to the EGFR leads to growth inhibition of tumor cells. Oncogene (1996) 13(2):275-282.
47. Steinberger P, Andris-Widhopf J, Buhler B, Torbett BE, Barbas CF 3rd: Functional deletion of the CCR5 receptor by intracellular immunization produces cells that are refractory to CCR5-dependent HIV-1 infection and cell fusion. Proc Natl Acad Sci USA (2000) 97(2):805-810.
48. Figini M, Ferri R, Mezzanzanica D, Bagnoll M, Luison E, Miotti S, Canevari S: Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies. Gene Ther(2003) 10(12):1018-1025.
49. Jendreyko N, Popkov M, Beerli RR, Chung J, McGavern DB, Rader C, Barbas CF 3rd: Intradiabodies, bispecific, tetravalent antibodies for the simultaneous functional knockout of two cell surface receptors. J Biol Chem (2003) 278(48):47812-47819.
50. Wheeler YY, Kute TE, Willingham MC, Chen SY, Sane DC: Intrabody-based strategies for inhibition of vascular endothelial growth factor receptor-2: Effects on apoptosis, cell growth, and angiogenesis. FASEB J (2003) 17(12):1733-1735.
51. zu Putlitz J, Skerra A, Wands JR: Intracellular expression of a cloned antibody fragment interferes with hepatitis B virus surface antigen secretion. Biochem Biophys Res Commun (1999) 255(3):785-791.
52. Legastelois I, Desgranges C: Design and intracellular activity of a human single-chain antibody to human immunodeficiency virus type 1 conserved gp41 epitope. J Virol (2000) 74(12):5712-5715.
53. Wang T, Li JD, Li C, Liang MF, Li DX: Construction and stable expression of intracellular antibodies to glycoprotein of hantavirus. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi (2003) 17(2):116-120.
54. Busch A, Marasco WA, Doebis C, Volk HD, Seifert M: MHC class I manipulation on cell surfaces by gene transfer of anti-MHC class I intrabodies - a tool for decreased immunogenicity of allogeneic tissue and cell transplants. Methods (2004) 34(2):240-249.
55. Beyer F, Doebis C, Busch A, Ritter T, Mhashilkar A, Marasco WM, Laube H, Volk HD, Seifert M: Decline of surface MHC I by adenoviral gene transfer of anti-MHC I intrabodies in human endothelial cells-new perspectives for the generation of universal donor cells for tissue transplantation. J Gene Med (2004) 6(6):616-623.
56. Lener M, Horn IR, Cardinale A, Messina S, Nielsen UB, Rybak SM, Hoogenboom HR, Cattaneo A, Biocca S: Diverting a protein from its cellular location by intracellular antibodies. The case of p21Ras. Eur J Biochem (2000) 267(4):1196-1205.
57. Sibler AP, Courtete J, Muller CD, Zeder-Lutz G, Weiss E: Extended half-life upon binding of destabilized intrabodies allows specific detection of antigen in mammalian cells. FEBS J (2005) 272(11):2878-2891.
58. Tse E, Rabbitts TH: Intracellular antibody-caspase-mediated cell killing: An approach for application in cancer therapy. Proc Natl Acad Sci USA (2000) 97(22):12266-12271.
59. Alting-Mees MA, Risseeuw EP, Liu E, Desautels M, Crosby WA, Hemmingsen SM: Intracellular expression of recombinant antibody fluorescent protein fusions for localization of target antigens in Schizosaccharomyces pombe. Methods Mol Biol (2005) 313:97-106.
60. Sachse C, Krausz E, Kronke A, Hannus M, Walsh A, Grabner A, Ovcharenko D, Dorris D, Trudel C, Sonnichsen B, Echeverri CJ: High-throughput RNA interference strategies for target discovery and validation by using synthetic short interfering RNAs: Functional genomics investigations of biological pathways. Methods Enzymol (2005) 392:242-277.
61. Couzin J: Molecular biology. RNAI shows cracks in its armor. Science (2004) 306(5699):1124-1125.
62. Groves MA, Osbourn JK: Applications of ribosome display to antibody drug discovery. Expert Opin Biol Ther (2005) 5(1):125-135.
63. Odegrip R, Coomber D, Eldridge B, Hederer R, Kuhlman PA, Ullman C, FitzGerald K, McGregor D: CIS display: In vitro selection of peptides from libraries of protein-DNA complexes. Proc Natl Acad Sci USA (2004) 101(9):2806-2810.
64. Reiersen H, Lobersli I, Loset GA, Hvattum E, Simonsen B, Stacy JE, McGregor D, Fitzgerald K, Weischof M, Brekke OH, Marvik OJ: Covalent antibody display - an in vitro antibody-DNA library selection system. Nucleic Acids Res (2005) 33(1):e10.
65. Popkov M, Jendreyko N, McGavern DB, Rader C, Barbas CF, 3rd: Targeting tumor angiogenesis with adenovirus-delivered anti-Tle-2 intrabody. Cancer Res (2005) 65(3):972-981.
66. van Etten B, ten Hagen TL, de Vries MR, Ambagtsheer G, Huet T, Eggermont AM: Prerequisites for effective adenovirus mediated gene therapy of colorectal liver metastases in the rat using an intracellular neutralizing antibody fragment to p21-Ras. Br J Cancer (2002) 86(3):436-442.
67. Alvarez RD, Barnes MN, Gomez-Navarro J, Wang M, Strong TV, Arafat W, Arani RB, Johnson MR, Roberts BL, Siegal GP, Curiel DT: A cancer gene therapy approach utilizing an anti-ErbB-2 single-chain antibody-encoding adenovirus (AD21): A phase I trial. Clin Cancer Res (2000) 6(8):3081-3087.
68. Conwell CC, Huang L: Recent advances in non-viral gene delivery. Adv Genet (2005) 53PA:1-18.
69. Matsushita M, Matsui H: Protein transduction technology. J Mol Med (2005) 83(5):324-328.
70. Heng BC, Kemeny DM, Liu H, Cao T: Potential applications of intracellular antibodies (intrabodies) in stem cell therapeutics. J Cell Mol Med (2005) 9(1):191-195.
71. Zemel R, Berdichevsky Y, Bachmatov L, Benhar I, Tur-Kaspa R: Inhibition of hepatitis C virus NS3-mediated cell transformation by recombinant intracellular antibodies. J Hepatol (2004) 40(6):1000-1007.
72. Gal-Tanamy M, Zemel R, Berdichevsky Y, Bachmatov L, Tur-Kaspa R, Benhar I: HCV NS3 serine protease-neutralizing single-chain antibodies isolated by a novel genetic screen. J Mol Biol (2005) 347(5):991-1003.
73. Jin YH, Kwon MH, Kim K, Shin HJ, Shin JS, Cho H, Park S: An intracellular antibody can suppress tumorigenicity in hepatitis B virus X-expressing cells. Cancer Immunol Immunother (2005):doi:10.1007/s00262-005-0037-2.
74. Accardi L, Dona MG, Di Bonito P, Giorgi C: Intracellular anti-E7 human antibodies in single-chain format inhibit proliferation of HPV16-positive cervical carcinoma cells. Int J Cancer (2005) 116(4):564-570.
75. Vascotto F, Visintin M, Cattaneo A, Burrone OR: Design and selection of an intrabody library produced de-novo for the non-structural protein NSP5 of rotavirus. J Immunol Methods (2005) 301(1-2):31-40.
76. Vetrugno V, Cardinate A, Filesi I, Mattei S, Sy MS, Pocchiari M, Biocca S: KDEL-tagged anti-prion intrabodies impair PrP lysosomal degradation and inhibit scrapie infectivity. Biochem Biophys Res Commun (2005) 338(4):1791-1797.
77. Wolfgang WJ, Miller TW, Webster JM, Huston JS, Thompson LM, Marsh JL, Messer A: Suppression of Huntingdon's disease pathology in Drosophila bY human single-chain Fv antibodies. Proc Natl Acad Sci USA (2005) 102(32):11563-11568.
78. Miller TW, Zhou C, Gines S, MacDonald ME, Mazarakis ND, Bates GP, Huston JS, Messer A: A human single-chain Fv intrabody preferentially targets amino-terminal Huntingtin's fragments in striatal models of Huntingdon's disease. Neurobiol Dis (2005) 19(1-2):47-56.
79. Paganetti P, Calanca V, Galli C, Stefani M, Molinari M: β-Site specific intrabodies to decrease and prevent generation of Alzheimer's Aβ peptide. J Cell Biol (2005) 168(6):863-868.
80. Zhou C, Emadi S, Sierks MR, Messer A: A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed α-synuclein. Mol Ther (2004) 10(6):1023-1031.
81. Jendreyko N, Popkov M, Rader C, Barbas CF 3rd: Phenotypic knockout of VEGF-R2 and Tie-2 with an intradiabody reduces tumor growth and angiogenesis in vivo. Proc Natl Acad Sci USA (25) 102(23):8293-8298.