immunoglobulin fragments


Summary: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.

Top Publications

  1. Roth A, Drummond D, Conrad F, Hayes M, Kirpotin D, Benz C, et al. Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells. Mol Cancer Ther. 2007;6:2737-46 pubmed
    ..Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs. ..
  2. Huang L, Muyldermans S, Saerens D. Nanobodies®: proficient tools in diagnostics. Expert Rev Mol Diagn. 2010;10:777-85 pubmed publisher
    ..Here we present several examples of currently available applications of Nanobodies to the field of immunosensor for cancer, immunoaffinity chromatography, in vivo and intracellular imaging. ..
  3. Stirnemann K, Romero J, Baldi L, Robert B, Cesson V, Besra G, et al. Sustained activation and tumor targeting of NKT cells using a CD1d-anti-HER2-scFv fusion protein induce antitumor effects in mice. J Clin Invest. 2008;118:994-1005 pubmed publisher
    ..Targeting iNKT cells to the tumor site thus may activate a combined innate and adaptive immune response that may prove to be effective in cancer immunotherapy. ..
  4. An F, Drummond D, Wilson S, Kirpotin D, Nishimura S, Broaddus V, et al. Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies. Mol Cancer Ther. 2008;7:569-78 pubmed publisher
  5. Garaicoechea L, Olichon A, Marcoppido G, Wigdorovitz A, Mozgovoj M, Saif L, et al. Llama-derived single-chain antibody fragments directed to rotavirus VP6 protein possess broad neutralizing activity in vitro and confer protection against diarrhea in mice. J Virol. 2008;82:9753-64 pubmed publisher
    ..Neutralizing VHH directed to VP6 promise to become an essential tool for the prevention and treatment of rotavirus diarrhea...
  6. Turunen L, Takkinen K, Söderlund H, Pulli T. Automated panning and screening procedure on microplates for antibody generation from phage display libraries. J Biomol Screen. 2009;14:282-93 pubmed publisher
  7. Douglas S, Bachelet I, Church G. A logic-gated nanorobot for targeted transport of molecular payloads. Science. 2012;335:831-4 pubmed publisher
    ..Our prototype could inspire new designs with different selectivities and biologically active payloads for cell-targeting tasks. ..
  8. Hust M, Dubel S, Schirrmann T. Selection of recombinant antibodies from antibody gene libraries. Methods Mol Biol. 2007;408:243-55 pubmed publisher
    ..Herein, methods are described for the selection of recombinant antibody fragments from naive antibody gene libraries. ..
  9. Wu A, Olafsen T. Antibodies for molecular imaging of cancer. Cancer J. 2008;14:191-7 pubmed publisher
    ..Antibody imaging can provide a sensitive, noninvasive means for molecular characterization of cell surface phenotype in vivo, which can in turn guide diagnosis, prognosis, therapy selection, and monitoring of treatment in cancer. ..

More Information


  1. Kogelberg H, Tolner B, Thomas G, Di Cara D, Minogue S, Ramesh B, et al. Engineering a single-chain Fv antibody to alpha v beta 6 integrin using the specificity-determining loop of a foot-and-mouth disease virus. J Mol Biol. 2008;382:385-401 pubmed publisher
  2. Kirsch M, Hülseweh B, Nacke C, Rülker T, Schirrmann T, Marschall H, et al. Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV). BMC Biotechnol. 2008;8:66 pubmed publisher
    ..The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak. ..
  3. Willemsen R, Chames P, Schooten E, Gratama J, Debets R. Selection of human antibody fragments directed against tumor T-cell epitopes for adoptive T-cell therapy. Cytometry A. 2008;73:1093-9 pubmed publisher
  4. Nelson A, Reichert J. Development trends for therapeutic antibody fragments. Nat Biotechnol. 2009;27:331-7 pubmed publisher
  5. He J, Wang Y, Feng J, Zhu X, Lan X, Iyer A, et al. Targeting prostate cancer cells in vivo using a rapidly internalizing novel human single-chain antibody fragment. J Nucl Med. 2010;51:427-32 pubmed publisher
  6. Nelson A. Antibody fragments: hope and hype. MAbs. 2010;2:77-83 pubmed
  7. Wu A. Antibodies and antimatter: the resurgence of immuno-PET. J Nucl Med. 2009;50:2-5 pubmed publisher
    ..Convergence of knowledge regarding key biomarkers that define normal biologic processes and disease with protein and imaging technology makes this an opportune time to revisit the combination of antibodies and PET, or immuno-PET. ..
  8. Cabezas S, Rojas G, Pavon A, Alvarez M, Pupo M, Guillen G, et al. Selection of phage-displayed human antibody fragments on Dengue virus particles captured by a monoclonal antibody: application to the four serotypes. J Virol Methods. 2008;147:235-43 pubmed
    ..The simple phage selection method on captured virus could be applied in a high throughput way to obtain larger panels of antibody fragments to Dengue virus for multiple applications. ..
  9. Jiang X, Burke V, Totrov M, Williams C, Cardozo T, Gorny M, et al. Conserved structural elements in the V3 crown of HIV-1 gp120. Nat Struct Mol Biol. 2010;17:955-61 pubmed publisher
    ..As these regions are targeted by cross-clade neutralizing human antibodies, they provide a blueprint for the design of vaccine immunogens that could elicit broadly cross-reactive protective antibodies. ..
  10. Shaw I, O Reilly A, Charleton M, Kane M. Development of a high-affinity anti-domoic acid sheep scFv and its use in detection of the toxin in shellfish. Anal Chem. 2008;80:3205-12 pubmed publisher
    ..Adjusting the cutoff point for DA concentration accordingly from the regulatory 20 mg/kg, the potential of the sheep scFv-based ELISA for use as a screening assay for DA in shellfish extracts was demonstrated. ..
  11. Gainkam L, Huang L, Caveliers V, Keyaerts M, Hernot S, Vaneycken I, et al. Comparison of the biodistribution and tumor targeting of two 99mTc-labeled anti-EGFR nanobodies in mice, using pinhole SPECT/micro-CT. J Nucl Med. 2008;49:788-95 pubmed publisher
    ..We compared the in vivo tumor uptake and biodistribution of 2 anti-epidermal growth factor receptor (anti-EGFR) Nanobodies, (99m)Tc-7C12 and (99m)Tc-7D12...
  12. Montgomery D, Wang Y, Hrin R, Luftig M, Su B, Miller M, et al. Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41. MAbs. 2009;1:462-74 pubmed
  13. Furrer E, Hulmann V, Urech D. Intranasal delivery of ESBA105, a TNF-alpha-inhibitory scFv antibody fragment to the brain. J Neuroimmunol. 2009;215:65-72 pubmed publisher
    ..Addition of a penetration enhancing peptide to the formulation enhanced the delivery of ESBA105 to the olfactory bulb and the cerebrum, without increasing systemic exposure. ..
  14. Harmsen M, van Solt C, Fijten H. Enhancement of toxin- and virus-neutralizing capacity of single-domain antibody fragments by N-glycosylation. Appl Microbiol Biotechnol. 2009;84:1087-94 pubmed publisher
    ..Thus, we have shown that N-glycosylation of VHHs contributes to toxin- and virus-neutralizing capacity. ..
  15. Deyev S, Lebedenko E. Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design. Bioessays. 2008;30:904-18 pubmed publisher
    ..Different multimerization strategies used now in antibody engineering make it possible to optimize biodistribution and tumor targeting of recombinant antibody constructs for cancer diagnostics and therapy. ..
  16. Kenanova V, Barat B, Olafsen T, Chatziioannou A, Herschman H, Braun J, et al. Recombinant carcinoembryonic antigen as a reporter gene for molecular imaging. Eur J Nucl Med Mol Imaging. 2009;36:104-14 pubmed publisher
    ..Biodistribution at 48 h demonstrated tumor uptake of 4.8 +/- 0.8%ID/g. The CEA N-A3 minigene has the potential to be used as a reporter gene for imaging cells in vivo. ..
  17. Leyton J, Olafsen T, Lepin E, Hahm S, Bauer K, Reiter R, et al. Humanized radioiodinated minibody for imaging of prostate stem cell antigen-expressing tumors. Clin Cancer Res. 2008;14:7488-96 pubmed publisher
    ..Imaging PSCA-positive prostate cancer is feasible using an intermediate size antibody fragment at 21 hours. ..
  18. Verheesen P, Roussis A, de Haard H, Groot A, Stam J, den Dunnen J, et al. Reliable and controllable antibody fragment selections from Camelid non-immune libraries for target validation. Biochim Biophys Acta. 2006;1764:1307-19 pubmed
  19. Kenanova V, Olafsen T, Williams L, Ruel N, Longmate J, Yazaki P, et al. Radioiodinated versus radiometal-labeled anti-carcinoembryonic antigen single-chain Fv-Fc antibody fragments: optimal pharmacokinetics for therapy. Cancer Res. 2007;67:718-26 pubmed
    ..Finally, the 125I/111In biodistribution data allowed for dose estimations, which suggest the 131I-labeled scFv-Fc H310A/H435Q as a promising candidate for radioimmunotherapy. ..
  20. Goldman E, Anderson G, Liu J, Delehanty J, Sherwood L, Osborn L, et al. Facile generation of heat-stable antiviral and antitoxin single domain antibodies from a semisynthetic llama library. Anal Chem. 2006;78:8245-55 pubmed
    ..The ability to rapidly select such rugged antibodies will enhance the reliability of immunoassays by extending shelf life and the capacity to function in hostile environments...
  21. Dufner P, Jermutus L, Minter R. Harnessing phage and ribosome display for antibody optimisation. Trends Biotechnol. 2006;24:523-9 pubmed
    ..This review introduces the two technologies, compares them with respect to their use in antibody optimisation and highlights how they can be exploited for the successful and efficient generation of putative drug candidates. ..
  22. Sibler A, Courtête J, Muller C, Zeder Lutz G, Weiss E. Extended half-life upon binding of destabilized intrabodies allows specific detection of antigen in mammalian cells. FEBS J. 2005;272:2878-91 pubmed
  23. Holliger P, Hudson P. Engineered antibody fragments and the rise of single domains. Nat Biotechnol. 2005;23:1126-36 pubmed
  24. Gould L, Sui J, Foellmer H, Oliphant T, Wang T, Ledizet M, et al. Protective and therapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virus. J Virol. 2005;79:14606-13 pubmed
    ..These recombinant human scFvs are potential candidates for immunoprophylaxis and therapy of flavivirus infections. ..
  25. Almquist K, McLean M, Niu Y, Byrne G, Olea Popelka F, Murrant C, et al. Expression of an anti-botulinum toxin A neutralizing single-chain Fv recombinant antibody in transgenic tobacco. Vaccine. 2006;24:2079-86 pubmed
    ..Transgenic plants could provide an inexpensive production platform for expression of multiple mAbs toward the creation of polyclonal therapies (i.e. pooled mAbs) as the next improvement in recombinant antibody therapy. ..
  26. Rahbarizadeh F, Rasaee M, Forouzandeh M, Allameh A. Over expression of anti-MUC1 single-domain antibody fragments in the yeast Pichia pastoris. Mol Immunol. 2006;43:426-35 pubmed
    ..pastoris is a suitable host for high level and correctly folded production of VHH antibody fragments with potential in vivo diagnostic and therapeutic applications. This is the first report of expression of VHH in P. pastoris. ..
  27. Hu S, Li L, Qiao J, Guo Y, Cheng L, Liu J. Codon optimization, expression, and characterization of an internalizing anti-ErbB2 single-chain antibody in Pichia pastoris. Protein Expr Purif. 2006;47:249-57 pubmed
    ..Functional studies showed that the A21 scFv could be internalized with high efficiency after binding to the ErbB2-overexpressing cells, suggesting this regent may prove especially useful for ErbB2-targeted immunotherapy. ..
  28. Persson H, Lantto J, Ohlin M. A focused antibody library for improved hapten recognition. J Mol Biol. 2006;357:607-20 pubmed
    ..The study supports the notion that it is possible to create antibody libraries that are biased for the recognition of antigens of pre-defined size. ..
  29. Harmsen M, van Solt C, van Zijderveld van Bemmel A, Niewold T, van Zijderveld F. Selection and optimization of proteolytically stable llama single-domain antibody fragments for oral immunotherapy. Appl Microbiol Biotechnol. 2006;72:544-51 pubmed
    ..K922 is thus a promising candidate for prevention of piglet diarrhoea. Furthermore, our findings could guide selection and improvement by genetic engineering of other recombinant antibody fragments for oral use...
  30. Liu R, Zhou C, Wang D, Ma W, Lin C, Wang Y, et al. Enhancement of DNA vaccine potency by sandwiching antigen-coding gene between secondary lymphoid tissue chemokine (SLC) and IgG Fc fragment genes. Cancer Biol Ther. 2006;5:427-34 pubmed
  31. Hu X, O Hara L, White S, Magner E, Kane M, Wall J. Optimisation of production of a domoic acid-binding scFv antibody fragment in Escherichia coli using molecular chaperones and functional immobilisation on a mesoporous silicate support. Protein Expr Purif. 2007;52:194-201 pubmed
    ..The work outlines the potential benefit of applying a molecular chaperone/folding catalyst screening approach to improve antibody fragment production for applications such as sensor development. ..
  32. Harmsen M, Van Solt C, Fijten H, Van Setten M. Prolonged in vivo residence times of llama single-domain antibody fragments in pigs by binding to porcine immunoglobulins. Vaccine. 2005;23:4926-34 pubmed
    ..Four pIgG-binding VHH2s were administered to pigs and showed a 100-fold extended in vivo residence times as compared to a control VHH2 that does not bind to pIgG. This could provide the basis for therapeutic application of VHHs in pigs...
  33. Emberson L, Trivett A, Blower P, Nicholls P. Expression of an anti-CD33 single-chain antibody by Pichia pastoris. J Immunol Methods. 2005;305:135-51 pubmed
    ..Flow cytometry and Biacore analysis demonstrated binding to target antigen CD33 on the surface of human leukaemic cell line HL-60, and to recombinant soluble CD33 respectively. ..
  34. Hoogenboom H. Selecting and screening recombinant antibody libraries. Nat Biotechnol. 2005;23:1105-16 pubmed
  35. Wu A, Senter P. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol. 2005;23:1137-46 pubmed
    ..Nonetheless, highly promising results from preclinical models will continue to drive the clinical development of this therapeutic class. ..
  36. Lamberski J, Thompson N, Burgess R. Expression and purification of a single-chain variable fragment antibody derived from a polyol-responsive monoclonal antibody. Protein Expr Purif. 2006;47:82-92 pubmed
    ..The polyol-responsiveness of the scFv was determined by an ELISA-elution assay. Although the scFv loses considerable affinity for its antigen, it maintains similar polyol-responsiveness as the parent monoclonal antibody, PR-mAb NT73. ..
  37. Hu X, Spada S, White S, Hudson S, Magner E, Wall J. Adsorption and activity of a domoic acid binding antibody fragment on mesoporous silicates. J Phys Chem B. 2006;110:18703-9 pubmed
    ..The antigen:antibody ratio decreased from 1:1.3 to <1:10 with increasing concentration of immobilized antibody, and the immobilized scFv exhibited no detectable reduction in domoic acid binding over a 42-day incubation period. ..
  38. Kubetzko S, Balic E, Waibel R, Zangemeister Wittke U, Plückthun A. PEGylation and multimerization of the anti-p185HER-2 single chain Fv fragment 4D5: effects on tumor targeting. J Biol Chem. 2006;281:35186-201 pubmed
    ..Both multimerization and PEGylation represent thus useful strategies to tailor the pharmacokinetic properties of therapeutic antibodies and their combined use can additively improve tumor targeting. ..
  39. Ackerson C, Jadzinsky P, Jensen G, Kornberg R. Rigid, specific, and discrete gold nanoparticle/antibody conjugates. J Am Chem Soc. 2006;128:2635-40 pubmed
    ..A complex of the MPC-scFv conjugate with the neuraminidase was isolated, and the presence of four gold clusters was verified by cryoelectron microscopy. ..
  40. Simmons D, Abregu F, Krishnan U, Proll D, Streltsov V, Doughty L, et al. Dimerisation strategies for shark IgNAR single domain antibody fragments. J Immunol Methods. 2006;315:171-84 pubmed
  41. van der Vaart J, Pant N, Wolvers D, Bezemer S, Hermans P, Bellamy K, et al. Reduction in morbidity of rotavirus induced diarrhoea in mice by yeast produced monovalent llama-derived antibody fragments. Vaccine. 2006;24:4130-7 pubmed
    ..They could provide a treatment modality for the moderation of human rotavirus infections having a significant impact on the course of an often fatal childhood disease...
  42. Huang B, Davern S, Kennel S. Mono and bivalent binding of a scFv and covalent diabody to murine laminin-1 using radioiodinated proteins and SPR measurements: effects on tissue retention in vivo. J Immunol Methods. 2006;313:149-60 pubmed
  43. Pelat T, Hust M, Laffly E, Condemine F, Bottex C, Vidal D, et al. High-affinity, human antibody-like antibody fragment (single-chain variable fragment) neutralizing the lethal factor (LF) of Bacillus anthracis by inhibiting protective antigen-LF complex formation. Antimicrob Agents Chemother. 2007;51:2758-64 pubmed
    ..These results, and others formerly published, demonstrate that our approach can generate antibody fragments suitable for prophylaxis and therapeutics. ..
  44. Duan J, Ji X, Feng J, Han W, Zhang P, Cao W, et al. A human neutralizing antibody against a conformational epitope shared by oligomeric SARS S1 protein. Antivir Ther. 2006;11:117-23 pubmed
    ..This study should aid in the manufacture of neutralizing antibody, provide a better understanding the immunological characteristics of SARS protein and facilitate the design of a SARS vaccine. ..
  45. Seo H, Masuoka M, Murofushi H, Takeda S, Shibata T, Ohta K. Rapid generation of specific antibodies by enhanced homologous recombination. Nat Biotechnol. 2005;23:731-5 pubmed
  46. Hu X, O Dwyer R, Wall J. Cloning, expression and characterisation of a single-chain Fv antibody fragment against domoic acid in Escherichia coli. J Biotechnol. 2005;120:38-45 pubmed
    ..The purified scFv exhibited binding similar to the parent monoclonal antibody and is being used to develop an immunosensor to detect domoic acid in contaminated shellfish samples. ..
  47. Krüger C, Hultberg A, Marcotte H, Hermans P, Bezemer S, Frenken L, et al. Therapeutic effect of llama derived VHH fragments against Streptococcus mutans on the development of dental caries. Appl Microbiol Biotechnol. 2006;72:732-7 pubmed
    ..No additional therapeutic effect of GOx was observed. Our results suggest that llama VHH antibodies may be a potential benefit as prophylaxis against dental caries...
  48. Sandee D, Tungpradabkul S, Kurokawa Y, Fukui K, Takagi M. Combination of Dsb coexpression and an addition of sorbitol markedly enhanced soluble expression of single-chain Fv in Escherichia coli. Biotechnol Bioeng. 2005;91:418-24 pubmed
    ..coli by the Dsb coexpression system with the addition of sorbitol medium additive. This method might be applicable for high-yield soluble expression of proteins with multiple disulfide bonds. ..
  49. Thomassen Y, Verkleij A, Boonstra J, Verrips C. Specific production rate of VHH antibody fragments by Saccharomyces cerevisiae is correlated with growth rate, independent of nutrient limitation. J Biotechnol. 2005;118:270-7 pubmed
    ..From our results we conclude that to obtain a maximal amount of VHH per kilogram biomass per hour, VHH production should be done in carbon limited continuous cultures at high specific growth rates. ..
  50. Olafsen T, Kenanova V, Sundaresan G, Anderson A, Crow D, Yazaki P, et al. Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo imaging. Cancer Res. 2005;65:5907-16 pubmed
    ..1 +/- 1.5% ID/g). Thus, by manipulating the size and format of anti-p185(HER2) antibody fragments, the kidney activity was reduced and high or low expression of p185HER2 in xenografts could be distinguished by microPET imaging. ..
  51. Donà M, Giorgi C, Accardi L. Characterization of antibodies in single-chain format against the E7 oncoprotein of the human papillomavirus type 16 and their improvement by mutagenesis. BMC Cancer. 2007;7:25 pubmed
    ..ScFv43 M2 shows higher thermal stability with respect to the parental scFv43, and scFv51 shows high stability and solubility. These properties make the 2 scFvs the best candidates to be tested for anti-E7 activity in vivo. ..
  52. Harmsen M, de Haard H. Properties, production, and applications of camelid single-domain antibody fragments. Appl Microbiol Biotechnol. 2007;77:13-22 pubmed
    ..This minireview offers an overview of (1) their properties as compared to conventional antibodies, (2) their production in microorganisms, with a focus on yeasts, and (3) their therapeutic applications...
  53. Coelho V, Dernedde J, Petrausch U, Panjideh H, Fuchs H, Menzel C, et al. Design, construction, and in vitro analysis of A33scFv::CDy, a recombinant fusion protein for antibody-directed enzyme prodrug therapy in colon cancer. Int J Oncol. 2007;31:951-7 pubmed
    ..These results demonstrate bifunctional activity of the heterogeneous Pichia-produced A33scFv::CDy fusion protein and proof of principle for the ADEPT system proposed herein. ..