Skip to main content

Advertisement

Log in

Catalytic antibodies and their applications in biotechnology: state of the art

  • Review
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Catalytic antibodies are immunoglobulins endowed with enzymatic properties. Discovered in the second part of the 1980s, the enthusiasm they initially aroused was counterbalanced by the difficulty of their production and their low catalytic rates. Nevertheless, improvements in expression systems and engineering technologies, combined with various studies suggesting that catalytic antibodies play a role in the immune system, have opened the way to new applications for these proteins. Herein we review catalytic antibodies from a biotechnological point of view, focusing our study on the different production methods, expression systems and their potential clinical applications dedicated to these proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ali M, Suzuki H, Fukuba T, Jiang X, Nakano H, Yamane T (2005) Improvements in the cell-free production of functional antibodies using cell extract from protease-deficient Escherichia coli. J Biosci Bioeng 99:181–186

    Article  CAS  PubMed  Google Scholar 

  • Avalle B, Thomas D, Friboulet A (1998) Functional mimicry : elicitation of a monoclonal anti-idiotypic antibody hydrolysing β-lactams. FASEB J 12:1055–1060

    CAS  PubMed  Google Scholar 

  • Ben Naya R, Matti K, Guellier A, Matagne A, Boquet D, Thomas D, Friboulet A, Avalle B, Padiolleau-Lefèvre S (2013) Efficient refolding of a recombinant abzyme : structural and catalytic characterizations. Appl Microbiol Biotechnol 97:7721–7731

    Article  CAS  PubMed  Google Scholar 

  • Berkmen M (2012) Production of disulfide-bonded proteins in Escherichia coli. Prot Expr Purif 82:240–251

    Article  CAS  Google Scholar 

  • Bowdish K, Tang Y, Hicks JB, Hilvert D (1991) Yeast expression of a catalytic antibody with chorismate mutase activity. J Biol Chem 18:11901–11908

    Google Scholar 

  • Briscoe RJ, Jeanville PM, Cabrera C, Baird TJ, Woods JH, Landry DW (2001) A catalytic antibody against cocaïne attenuates cocaine’s cardiovascular effects in mice: a dose and time course analysis. Int Immunopharmacol 1:1189–1198

    Article  CAS  PubMed  Google Scholar 

  • Cai X, Whitfield T, Hixon MS, Grant Y, Koob GF, Janda KD (2013) Probing active cocaïne vaccination performance through catalytic and noncatalytic hapten design. J Med Chem 56:3701–3709

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Deng SX, de Prada P, Landry DW (2002) Anticocaine catalytic antibodies. J Immunol Methods 269:299–310

    Article  CAS  PubMed  Google Scholar 

  • Dickerson TJ, Yamamoto N, Janda KD (2004) Antibody-catalytzed oxidative dégradation of nicotine using riboflavin. Bioorg Med Chem 12:4981–4987

    Article  CAS  PubMed  Google Scholar 

  • Gibbs RA, Posner BA, Filpula DR, Dodd SW, Finkelman MAJ, Lee TK, Wroble M, Whitlow M, Benkovic SJ (1991) Construction and characterization of a single-chain catalytic antibody. Proc Natl Acad Sci USA 88:4001–4004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gonçalves O, Dintinger T, Blanchard D, Tellier C (2002) Functional mimicry between anti-tendamistat antibodies and α-amylase. J Immunol Methods 269:29–37

    Article  PubMed  Google Scholar 

  • Gorelick DA (2012) Pharmacokinetic strategies for treatment of drug overdose and addiction. Future Med Chem 4:227–243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Goswami RK, Huang ZZ, Forsyth JS, Felding-Habermann B, Sinha SC (2009) Multiple catalytic aldolase antibodies suitable for chemical programming. Bioorg Med Chem Lett 19:3821–3824

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hifumi E, Morihara F, Hatiuchi K, Okuda T, Nishizono A, Uda T (2008) Catalytic features and eradication ability of antibody light chain UA15-L against H. pylori. J Biol Chem 283:899–907

    Article  CAS  PubMed  Google Scholar 

  • Hifumi E, Higashi K, Uda T (2010) Catalytic digestion of human tumor necrosis factor-α by antibody heavy chain. FEBS J 277:3823–3832

    Article  CAS  PubMed  Google Scholar 

  • Hifumi E, Honjo E, Fujimoto N, Arakawa M, Nishizono A, Uda T (2013) Highly efficient method of preparing human catalytic antibody light chains and their biological characteristics. FASEB J 26:1607–1615

    Article  Google Scholar 

  • Hilvert D, Carpenter SH, Nared KD, Auditor MT (1988) Catalysis of concerted reactions by antibodies: the Claisen rearrangement. Proc Natl Acad Sci USA 85:4953–4955

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hu R, Xie GY, Zhang X, Guo ZQ, Jin S (1998) Production and characterization of monoclonal anti-idiotypic antibody exhibiting a catalytic activity similar to carboxypeptidase. J Biotechnol 61:109–115

    Article  CAS  PubMed  Google Scholar 

  • Izadyar L, Friboulet A, Remy MH, Roseto A, Thomas D (1993) Monoclonal anti-idiotypic antibodies as functional internal images of enzyme active sites: production of a catalytic antibody with a cholinesterase activity. Proc Natl Acad Sci USA 90:8876–8880

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Janda KD, Weinhouse MI, Schloeder DM, Lerner RA, Benkovic SJ (1990) Bait and switch strategy for obtaining catalytic antibodies with acyl-transfer capabilities. J Am Chem Soc 112:1274–1275

    Article  CAS  Google Scholar 

  • Jang C, Machtaler S, Matsuuchi L (2010) The role of Ig-α/β in B cell antigen receptor internalization. Immunol Lett 134:75–82

    Article  CAS  PubMed  Google Scholar 

  • Jencks WP (1969) Catalysis in chemistry and enzymology. Mc-Graw-Hill Book Co. Inc., New York

    Google Scholar 

  • Jerne NK (1974) Towards a network theory of the immune system. Annu Immunol (Paris). 125C:373–389

    CAS  Google Scholar 

  • Jiang XP, Ookubo Y, Fujii I, Nakano H, Yamane T (2002) Expression of Fab fragment of catalytic antibody 6D9 in an Escherichia coli in vitro coupled transcription/translation system. FEBS Lett 514:290–294

    Article  CAS  PubMed  Google Scholar 

  • Kim SH, Schindler DG, Lindner AB, Tawfik DS, Eshhar Z (1997) Expression and characterization of recombinant single-chain Fv and Fv fragments derived from a set of catalytic antibodies. Mol Immunol 34:891–906

    Article  CAS  PubMed  Google Scholar 

  • Kohler G, Milstein C (1975) Continuous culture of fused cells secreting antibody or predefined specificity. Nature 256:495–497

    Article  CAS  PubMed  Google Scholar 

  • Kozyr AV, Bobik TV, Ignatova AN, Kolesnikov AV (2004) Production of DNA-hydrolyzing antibody BV04-01 Fab fragment in methylotrophic yeast Pichia pastoris. Mol Biol 38:914–920

    Article  CAS  Google Scholar 

  • Kurkova IN, Reshetnyak AV, Durova OM, Knorre VD, Tramontano A, Friboulet A, Ponomarenko NA, Gabibov AG, Smirnov IV (2009) Antibodies-antidotes against organophosphorus compounds. Dokl Akad Nauk 425:549–552

    Google Scholar 

  • Lee WR, Jang JY, Kwon MH, Kim YS (2010) Gene silencing by cell-penetrating, sequence-selective and nucleic-acid hydrolyzing antibodies. Nucleic Acids Res 38:1596–1609

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li JW, Xia L, Su Y, Liu H, Xia X, Lu Q, Yand C, Reheman K (2012) Molecular imprint of enzyme active site by camel nanobodies : rapid and efficient approach to produce abzyme with aliinase activity. J Biol Chem 287:13713–13721

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McKenzie KM, Mee JM, Rogers CJ, Hixon MS, Kaufmann GF, Janda KD (2007) Identification and characterization of single chain anti-cocaine catalytic antibodies. J Mol Biol 365:722–731

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Padiolleau-Lefèvre S, Débat H, Phichith D, Thomas D, Friboulet A, Avalle B (2006) Expression of a functional scFv fragment of an anti-idiotypic antibody with a β-lactam hydrolytic activity. Immunol Lett 103:39–44

    Article  PubMed  Google Scholar 

  • Paul S, Planque S, Zhou XY, Taguchi H, Bathia G, Karle S, Hanson C, Nishiyama Y (2003) Specific HIV gp120-cleaving antibodies induced by covalently reactive analog of gp120. J Biol Chem 278:20429–20435

    Article  CAS  PubMed  Google Scholar 

  • Paul S, Planque S, Nishiyama Y (2010) Immunological origin and functional properties of catalytic autoantibodies to amyloid β peptide. J Clin Immunol 30:S43–S49

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pauling L (1948) Chemical achievement and hope for the future. Am Sci 36:51–58

    CAS  PubMed  Google Scholar 

  • Phichith D, Bun S, Padiolleau-Lefèvre S, Banh S, Thomas D, Friboulet A, Avalle B (2009) Mutational and inhibitory analysis of a catalytic antibody. Implication for drug discovery. Mol Immunol 47:348–356

    Article  CAS  PubMed  Google Scholar 

  • Pillet D, Paon M, Vorobiev II, Gabibov AG, Thomas D, Friboulet A (2002) Idiotypic network mimicry and antibody catalysis : lessons for the elicitation of efficient anti-idiotypic protease antibodies. J Immunol Methods 269:5–12

    Article  CAS  PubMed  Google Scholar 

  • Planque S, Nishiyama Y, Taguchi H, Salas M, Hanson C, Paul S (2008) Catalytic antibodies to HIV: physiological role and potential clinical utility. Autoimmun Rev 7:473–479

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pollack SJ, Jacobs JW, Schultz PG (1986) Selective chemical catalysis by an antibody. Science 234:1570–1573

    Article  CAS  PubMed  Google Scholar 

  • Ponomarenko NA, Pillet D, Paon M, Vorobiev II, Smirnov IV, Adenier H, Avalle B, Kolesnikov AV, Kozyr A, Thomas D, Gabibov AG, Friboulet A (2007) Anti-idiotypic antibody mimics proteolytic function of parent antigen. Biochemistry 46:14598–14609

    Article  CAS  PubMed  Google Scholar 

  • Rangan SK, Liu R, Brune D, Planque S, Paul S, Sierks MR (2003) Degradation of β-amyloid by proteolytic antibody light chains. Biochemistry 42:14328–14334

    Article  CAS  PubMed  Google Scholar 

  • Rao D, Wootla B (2007) Catalytic antibodies: concept and promise. Resonance (Springerlink) 12:6–21

    Article  CAS  Google Scholar 

  • Reshetnyak AV, Armentano MF, Ponomarenko NA, Vizzuso D, Durova OM, Ziganshin R, Serebryakova M, Govorun V, Gololobov G, Morse HC, Friboulet A, Makker SP, Gabibov AG, Tramontano A (2007) Routes to covalent catalysis by reactive selection for nascent protein nucleophiles. J Am Chem Soc 129:16175–16182

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Robin S, Petrov K, Dintinger T, Kujumdzieva A, Tellier C, Dion M (2003) Comparison of three microbial hosts for the expression of an active catalytic scFv. Mol Immunol 39:729–738

    Article  CAS  PubMed  Google Scholar 

  • Shamis M, Lode HN, Shabat D (2004) Bioactive of self-immolative dendritic prodrugs by catalytic antibody 38C2. J Am Chem Soc 126:1726–1731

    Article  CAS  PubMed  Google Scholar 

  • Sinha SC, Li LS, Miller GP, Dutta S, Rader C, Lerner RA (2004) Prodrugs of dynemicin analogs for selective chemotherapy mediated by an alodolase catalytic Ab. Proc Natl Acad Sci USA 101:3095–3099

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Smirnov I, Carletti E, Kurkova I, Nachon F, Nicolet Y, Mitkevich VA, Débat H, Avalle B, Belogurov AA, Kuznetsov N, Reshetnyak A, Masson P, Tonevitsky AG, Ponomarenko N, Makarov AA, Friboulet A, Tramontano A, Gabibov A (2011) Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics. Proc Natl Acad Sci USA 108:15954–15959

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stewart JD, Benkovic SJ (1995) Transition-state stabilization as a measure of the efficiency of antibody catalysis. Nature 375:388–391

    Article  CAS  PubMed  Google Scholar 

  • Taguchi H, Planque S, Nishiyama Y, Szabo P, Weksler ME, Friedland RP, Sudhir P (2008) Catalytic antibodies to amyloid β peptide in defense against Alzheimer disease. Autoimmun Rev 7:391–397

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Takahashi N, Kakinuma H, Liu L, Nishi Y, Fujii I (2001) In vitro abzyme evolution to optimize antibody recognition for catalysis. Nat Biotechnol 19:563–567

    Article  CAS  PubMed  Google Scholar 

  • Takahashi-Ando N, Kakinuma H, Fujii I, Nishi Y (2004) Directed evolution governed by controlling the molecular recognition between an abzyme and its haptenic transition-state analog. J Immunol Methods 294:1–14

    Article  CAS  PubMed  Google Scholar 

  • Tramontano A, Janda KD, Lerner R (1986) Chemical reactivity at an antibody binding site elicited by mechanistic design of a synthetic antigen. Proc Natl Acad Sci USA 89:7114–7118

    Google Scholar 

  • Treweek JB, Janda KD (2012) An antidote for acute cocaine toxicity. Mol Pharm 9:969–978

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wirsching P, Ashley JA, Lo CHL, Janda KD, Lerner RA (1995) Reactive immunization. Science 270:1775–1782

    Article  CAS  PubMed  Google Scholar 

  • Wootla B, Christophe OD, Mahendra A, Dimitrov JD, Repressé Y, Ollivier V, Friboulet A, Borel-Delon A, Levesque H, Borg JY, Andre S, Bayry J, Calvez T, Kaveri SV, Lacroix-Desmazes S (2011a) Proteolytic antibodies activate factor IX in patients with acquired haemophilia. Blood 117:2257–2264

    Article  CAS  PubMed  Google Scholar 

  • Wootla B, Lacroix-Desmazes S, Warrington AE, Bieber AJ, Kaveri S, Rodriguez M (2011b) Autoantibodies with enzymatic properties in human autoimmune diseases. J Autoimmun 37:144–150

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wörn A, Plückthun A (2001) Stability engineering of antibody single-chain Fv fragments. J Mol Biol 305:989–1010

    Article  PubMed  Google Scholar 

  • Xu Y, Yamamoto N, Janda K (2004) Catalytic antibodies: hapten design strategies and screening methods. Bioorg Med Chem 12:5247–5268

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Song J, Su J, Wei J, Yu Y, Lv S, Li W, Nie G (2010) A new human catalytic antibody Se-scFv-2D8 and its selenium-containing single domains with high GPX activity. J Mol Recognit 23:352–359

    Article  CAS  PubMed  Google Scholar 

  • Yin J, Li G, Ren X, Herrler G (2007) Select what you need: a comparative evaluation of the advantages and limitations of frequently used expression systems for foreign genes. J Biotechnol 127:335–347

    Article  CAS  PubMed  Google Scholar 

  • Zakharov AV, Smirnov IV, Serebryakova MV, Dronina MA, Kaznacheeva AV, Kurkova IN, Belogurov AA, Friboulet A, Ponomarenko NA, Gabibov AG, Bobik TV (2011) Expression of catalytic antibodies in eukaryotic systems. Mol Biol 45:86–95

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Séverine Padiolleau-Lefèvre.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Padiolleau-Lefèvre, S., Naya, R.B., Shahsavarian, M.A. et al. Catalytic antibodies and their applications in biotechnology: state of the art. Biotechnol Lett 36, 1369–1379 (2014). https://doi.org/10.1007/s10529-014-1503-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-014-1503-8

Keywords

Navigation