CoChat
Sign Up
Cited by 749Monoclonal and Polyclonal Antibodies ResearchNanoparticle-Based Drug DeliveryProtein purification and stability

The therapeutic potential of nanobodies

Open access
Jovčevska, Ivana, Muyldermans, Serge·2020·BioDrugs
DOI 10.1007/s40259-019-00392-zPMC PMC6985073
Open this paper in CoChat — free accountOpen PDF

Abstract

Today, bio-medical efforts are entering the subcellular level, which is witnessed with the fast-developing fields of nanomedicine, nanodiagnostics and nanotherapy in conjunction with the implementation of nanoparticles for disease prevention, diagnosis, therapy and follow-up. Nanoparticles or nanocontainers offer advantages including high sensitivity, lower toxicity and improved safety-characteristics that are especially valued in the oncology field. Cancer cells develop and proliferate in complex microenvironments leading to heterogeneous diseases, often with a fatal outcome for the patient. Although antibody-based therapy is widely used in the clinical care of patients with solid tumours, its efficiency definitely needs improvement. Limitations of antibodies result mainly from their big size and poor penetration in solid tissues. Nanobodies are a novel and unique class of antigen-binding fragments, derived from naturally occurring heavy-chain-only antibodies present in the serum of camelids. Their superior properties such as small size, high stability, strong antigen-binding affinity, water solubility and natural origin make them suitable for development into next-generation biodrugs. Less than 30 years after the discovery of functional heavy-chain-only antibodies, the nanobody derivatives are already extensively used by the biotechnology research community. Moreover, a number of nanobodies are under clinical investigation for a wide spectrum of human diseases including inflammation, breast cancer, brain tumours, lung diseases and infectious diseases. Recently, caplacizumab, a bivalent nanobody, received approval from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treatment of patients with thrombotic thrombocytopenic purpura.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s40259-019-00392-z

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Camelid VHH and shark V-NAR domains are used as templates to generate highly efficient and stable nanobodies.

    “Given their high-affinity, solubility and stability also in absence of the partner VL domain, the camelid VH domains (VHH) [4] and the shark VH domains called V-NAR (New Antigen Receptor) [5], are currently used as templates to generate highly efficient and stable new antibody fragments collectively termed nanobodies [6,7,8].”

    From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [6]

    The Introduction (“Nanobodies, the Smaller Variant of Antibodies”; page not provided) identifies camelid VHH domains as nanobodies and describes their affinity, solubility, and stability. It does not establish that shark V-NAR domains are used as templates for nanobodies; the shark-related material found is a reference title, not a finding of this paper. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 138

  1. [1]Baylin SB Ohm JE Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 2006 6 2 107 116 10.1038/nrc1799 16491070 · DOI
  2. [3]Jabir NR Anwar K Firoz CK Oves M Kamal MA Tabrez S An overview on the current status of cancer nanomedicines Curr Med Res Opin. 2018 34 5 911 921 10.1080/03007995.2017.1421528 29278015 · DOI
  3. [4]Lammers T Hennink WE Storm G Tumour-targeted nanomedicines: principles and practice Br J Cancer 2008 99 3 392 397 10.1038/sj.bjc.6604483 18648371 PMC2527811 · DOI
  4. [5]Wang MD Shin DM Simons JW Nie S Nanotechnology for targeted cancer therapy Expert Rev Anticancer Ther 2007 7 6 833 837 10.1586/14737140.7.6.833 17555393 · DOI
  5. [6]Van de Broek B Devoogdt N D’Hollander A Gijs HL Jans K Lagae L Specific cell targeting with nanobody conjugated branched gold nanoparticles for photothermal therapy ACS Nano. 2011 5 6 4319 4328 10.1021/nn1023363 21609027 · DOI
  6. [7]Tillib SV “Camel nanoantibody” is an efficient tool for research, diagnostics and therapy Mol Biol (Mosk) 2011 45 1 77 85 10.1134/S0026893311010134 21485499 · DOI
  7. [8]Padlan EA Anatomy of the antibody molecule Mol Immunol 1994 31 3 169 217 10.1016/0161-5890(94)90001-9 8114766 · DOI
  8. [9]Alexis F Rhee JW Richie JP Radovic-Moreno AF Langer R Farokhzad OC New frontiers in nanotechnology for cancer treatment Urol Oncol. 2008 26 1 74 85 10.1016/j.urolonc.2007.03.017 18190835 · DOI
  9. [10]Hu Y Liu C Muyldermans S Nanobody-based delivery systems for diagnosis and targeted tumor therapy Front Immunol. 2017 8 1442 10.3389/fimmu.2017.01442 29163515 PMC5673844 · DOI
  10. [11]Sunada H Magun BE Mendelsohn J MacLeod CL Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation Proc Natl Acad Sci USA 1986 83 11 3825 3829 10.1073/pnas.83.11.3825 2424012 PMC323616 · DOI
  11. [12]Li S Schmitz KR Jeffrey PD Wiltzius JJ Kussie P Ferguson KM Structural basis for inhibition of the epidermal growth factor receptor by cetuximab Cancer Cell 2005 7 4 301 311 10.1016/j.ccr.2005.03.003 15837620 · DOI
  12. [14]Weiner LM Surana R Wang S Monoclonal antibodies: versatile platforms for cancer immunotherapy Nat Rev Immunol 2010 10 5 317 327 10.1038/nri2744 20414205 PMC3508064 · DOI
  13. [15]Adams GP Weiner LM Monoclonal antibody therapy of cancer Nat Biotechnol 2005 23 9 1147 1157 10.1038/nbt1137 16151408 · DOI
  14. [16]Scott AM Allison JP Wolchok JD Monoclonal antibodies in cancer therapy Cancer Immun 2012 12 14 22896759 PMC3380347
  15. [17]Beckman RA Weiner LM Davis HM Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors Cancer. 2007 109 2 170 179 10.1002/cncr.22402 17154393 · DOI
  16. [18]Majidi J Barar J Baradaran B Abdolalizadeh J Omidi Y Target therapy of cancer: implementation of monoclonal antibodies and nanobodies Hum Antibodies. 2009 18 3 81 100 10.3233/HAB-2009-0204 19729803 · DOI
  17. [19]Epenetos AA Snook D Durbin H Johnson PM Taylor-Papadimitriou J Limitations of radiolabeled monoclonal antibodies for localization of human neoplasms Cancer Res 1986 46 6 3183 3191 3516393
  18. [20]Kolkman JA Law DA Nanobodies—from llamas to therapeutic proteins Drug Discov Today Technol 2010 7 2 e95 e146 10.1016/j.ddtec.2010.03.002 24103724 · DOI
  19. [21]Weinstein JN van Osdol W Early intervention in cancer using monoclonal antibodies and other biological ligands: micropharmacology and the “binding site barrier” Cancer Res 1992 52 9 Suppl 2747s 2751s 1563006
  20. [22]Juweid M Neumann R Paik C Perez-Bacete MJ Sato J van Osdol W Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier Cancer Res 1992 52 19 5144 5153 1327501
  21. [23]Adams GP Schier R McCall AM Simmons HH Horak EM Alpaugh RK High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules Cancer Res 2001 61 12 4750 4755 11406547
  22. [24]Cruz E Kayser V Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy Biologics. 2019 13 33 51 10.2147/BTT.S166310 31118560 PMC6503308 · DOI
  23. [25]Farajpour Z Rahbarizadeh F Kazemi B Ahmadvand D A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment Biochem Biophys Res Commun 2014 446 1 132 136 10.1016/j.bbrc.2014.02.069 24569074 · DOI
  24. [26]Tijink BM Laeremans T Budde M Stigter-van Walsum M Dreier T de Haard HJ Improved tumor targeting of anti-epidermal growth factor receptor nanobodies through albumin binding: taking advantage of modular nanobody technology Mol Cancer Ther 2008 7 8 2288 2297 10.1158/1535-7163.MCT-07-2384 18723476 · DOI
  25. [27]Ventola CL Progress in nanomedicine: approved and investigational nanodrugs Pharm Ther. 2017 42 12 742 755 PMC5720487 29234213
  26. [28]Miller MA Arlauckas S Weissleder R Prediction of anti-cancer nanotherapy efficacy by imaging Nanotheranostics. 2017 1 3 296 312 10.7150/ntno.20564 29071194 PMC5646731 · DOI · Paper page
  27. [29]Rizzo LY Theek B Storm G Kiessling F Lammers T Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications Curr Opin Biotechnol 2013 24 6 1159 1166 10.1016/j.copbio.2013.02.020 23578464 PMC3833836 · DOI
  28. [30]Peer D Karp JM Hong S Farokhzad OC Margalit R Langer R Nanocarriers as an emerging platform for cancer therapy Nat Nanotechnol. 2007 2 12 751 760 10.1038/nnano.2007.387 18654426 · DOI · Paper page
  29. [31]Maeda H Matsumura Y Tumoritropic and lymphotropic principles of macromolecular drugs Crit Rev Ther Drug Carrier Syst. 1989 6 3 193 210 2692843
  30. [32]Matsumura Y Maeda H A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs Cancer Res 1986 46 12 Pt 1 6387 6392 2946403
  31. [33]Zhan W Gedroyc W Xu XY The effect of tumour size on drug transport and uptake in 3-D tumour models reconstructed from magnetic resonance images PLoS One 2017 12 2 e0172276 10.1371/journal.pone.0172276 28212385 PMC5315397 · DOI
  32. [34]Thurber GM Dane Wittrup K A mechanistic compartmental model for total antibody uptake in tumors J Theor Biol. 2012 314 57 68 10.1016/j.jtbi.2012.08.034 22974563 PMC3729444 · DOI
  33. [35]Thurber GM Schmidt MM Wittrup KD Factors determining antibody distribution in tumors Trends Pharmacol Sci. 2008 29 2 57 61 10.1016/j.tips.2007.11.004 18179828 PMC2820301 · DOI
  34. [36]Wang L Huo M Chen Y Shi J Tumor microenvironment-enabled nanotherapy Adv Healthc Mater 2018 7 8 e1701156 10.1002/adhm.201701156 29283221 · DOI
  35. [37]Hamers-Casterman C Atarhouch T Muyldermans S Robinson G Hamers C Songa EB Naturally occurring antibodies devoid of light chains Nature. 1993 363 6428 446 448 10.1038/363446a0 8502296 · DOI · Paper page
  36. [38]Huang L Muyldermans S Saerens D Nanobodies(R): proficient tools in diagnostics Expert Rev Mol Diagn 2010 10 6 777 785 10.1586/erm.10.62 20843201 · DOI
  37. [39]Chakravarty R Goel S Cai W Nanobody: the “magic bullet” for molecular imaging? Theranostics. 2014 4 4 386 398 10.7150/thno.8006 24578722 PMC3936291 · DOI
  38. [40]Van Audenhove I Gettemans J Nanobodies as versatile tools to understand, diagnose, visualize and treat cancer EBioMedicine. 2016 8 40 48 10.1016/j.ebiom.2016.04.028 27428417 PMC4919472 · DOI
  39. [42]Muyldermans S Nanobodies: natural single-domain antibodies Annu Rev Biochem 2013 82 775 797 10.1146/annurev-biochem-063011-092449 23495938 · DOI · Paper page
  40. [43]Ingram JR Schmidt FI Ploegh HL Exploiting nanobodies’ singular traits Annu Rev Immunol 2018 36 695 715 10.1146/annurev-immunol-042617-053327 29490163 · DOI
  41. [44]Muyldermans S Baral TN Retamozzo VC De Baetselier P De Genst E Kinne J Camelid immunoglobulins and nanobody technology Vet Immunol Immunopathol 2009 128 1–3 178 183 10.1016/j.vetimm.2008.10.299 19026455 · DOI
  42. [46]Mitchell LS Colwell LJ Analysis of nanobody paratopes reveals greater diversity than classical antibodies Protein Eng Des Sel. 2018 31 7–8 267 275 10.1093/protein/gzy017 30053276 PMC6277174 · DOI · Paper page
  43. [48]Govaert J Pellis M Deschacht N Vincke C Conrath K Muyldermans S Dual beneficial effect of interloop disulfide bond for single domain antibody fragments J Biol Chem 2012 287 3 1970 1979 10.1074/jbc.M111.242818 22128183 PMC3283254 · DOI
  44. [49]Konning D Zielonka S Grzeschik J Empting M Valldorf B Krah S Camelid and shark single domain antibodies: structural features and therapeutic potential Curr Opin Struct Biol. 2017 45 10 16 10.1016/j.sbi.2016.10.019 27865111 · DOI · Paper page
  45. [50]Lauwereys M Arbabi Ghahroudi M Desmyter A Kinne J Holzer W De Genst E Potent enzyme inhibitors derived from dromedary heavy-chain antibodies EMBO J 1998 17 13 3512 3520 10.1093/emboj/17.13.3512 9649422 PMC1170688 · DOI
  46. [51]Beghein E Gettemans J Nanobody Technology: a versatile toolkit for microscopic imaging, protein–protein interaction analysis, and protein function exploration Front Immunol. 2017 8 771 10.3389/fimmu.2017.00771 28725224 PMC5495861 · DOI
  47. [52]van Koningsbruggen S de Haard H de Kievit P Dirks RW van Remoortere A Groot AJ Llama-derived phage display antibodies in the dissection of the human disease oculopharyngeal muscular dystrophy J Immunol Methods. 2003 279 1–2 149 161 10.1016/S0022-1759(03)00232-1 12969556 · DOI
  48. [53]Oliveira S Heukers R Sornkom J Kok RJ van Bergen PM Targeting tumors with nanobodies for cancer imaging and therapy J Controll Release 2013 172 3 607 617 10.1016/j.jconrel.2013.08.298 24035975 · DOI
  49. [54]De Vos J Devoogdt N Lahoutte T Muyldermans S Camelid single-domain antibody-fragment engineering for (pre)clinical in vivo molecular imaging applications: adjusting the bullet to its target Expert Opin Biol Ther 2013 13 8 1149 1160 10.1517/14712598.2013.800478 23675652 · DOI
  50. [56]Kunz P Zinner K Mucke N Bartoschik T Muyldermans S Hoheisel JD The structural basis of nanobody unfolding reversibility and thermoresistance Sci Rep 2018 8 1 7934 10.1038/s41598-018-26338-z 29784954 PMC5962586 · DOI
  51. [57]Arbabi-Ghahroudi M Tanha J MacKenzie R Prokaryotic expression of antibodies Cancer Metastasis Rev 2005 24 4 501 519 10.1007/s10555-005-6193-1 16408159 · DOI
  52. [58]Dmitriev OY Lutsenko S Muyldermans S Nanobodies as probes for protein dynamics in vitro and in cells J Biol Chem 2016 291 8 3767 3775 10.1074/jbc.R115.679811 26677230 PMC4759159 · DOI
  53. [59]Muyldermans S Cambillau C Wyns L Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains Trends Biochem Sci 2001 26 4 230 235 10.1016/S0968-0004(01)01790-X 11295555 · DOI
  54. [60]Klarenbeek A El Mazouari K Desmyter A Blanchetot C Hultberg A de Jonge N Camelid Ig V genes reveal significant human homology not seen in therapeutic target genes, providing for a powerful therapeutic antibody platform Mabs-Austin. 2015 7 4 693 706 10.1080/19420862.2015.1046648 PMC4622956 26018625 · DOI
  55. [61]Kijanka M Dorresteijn B Oliveira S van Bergen en Henegouwen PM Nanobody-based cancer therapy of solid tumors Nanomedicine (Lond). 2015 10 1 161 174 10.2217/nnm.14.178 25597775 · DOI
  56. [62]Vincke C Loris R Saerens D Martinez-Rodriguez S Muyldermans S Conrath K General strategy to humanize a camelid single-domain antibody and identification of a universal humanized nanobody scaffold J Biol Chem. 2009 284 5 3273 3284 10.1074/jbc.M806889200 19010777 · DOI
  57. [63]Romao E Morales-Yanez F Hu Y Crauwels M De Pauw P Hassanzadeh GG Identification of useful nanobodies by phage display of immune single domain libraries derived from camelid heavy chain antibodies Curr Pharm Des. 2016 22 43 6500 6518 10.2174/1381612822666160923114417 27669966 · DOI
  58. [64]Fernandes JC Therapeutic application of antibody fragments in autoimmune diseases: current state and prospects Drug Discov Today. 2018 23 12 1996 2002 10.1016/j.drudis.2018.06.003 29890227 · DOI
  59. [66]Schoonooghe S Laoui D Van Ginderachter JA Devoogdt N Lahoutte T De Baetselier P Novel applications of nanobodies for in vivo bio-imaging of inflamed tissues in inflammatory diseases and cancer Immunobiology. 2012 217 12 1266 1272 10.1016/j.imbio.2012.07.009 22884356 · DOI
  60. [67]Devoogdt N Xavier C Hernot S Vaneycken I D’Huyvetter M De Vos J Molecular imaging using nanobodies: a case study Methods Mol Biol. 2012 911 559 567 10.1007/978-1-61779-968-6_35 22886276 · DOI
  61. [68]Keyaerts M Xavier C Heemskerk J Devoogdt N Everaert H Ackaert C Phase I study of 68 Ga-HER2-nanobody for PET/CT assessment of HER2 expression in breast carcinoma J Nucl Med 2016 57 1 27 33 10.2967/jnumed.115.162024 26449837 · DOI
  62. [69]Hassanzadeh-Ghassabeh G Devoogdt N De Pauw P Vincke C Muyldermans S Nanobodies and their potential applications Nanomedicine (Lond). 2013 8 6 1013 1026 10.2217/nnm.13.86 23730699 · DOI
  63. [70]Debie P Devoogdt N Hernot S Targeted nanobody-based molecular tracers for nuclear imaging and image-guided surgery Antibodies. 2019 8 1 12 10.3390/antib8010012 PMC6640687 31544818 · DOI
  64. [71]Xavier C Vaneycken I D’Huyvetter M Heemskerk J Keyaerts M Vincke C Synthesis, preclinical validation, dosimetry, and toxicity of 68 Ga-NOTA-anti-HER2 Nanobodies for iPET imaging of HER2 receptor expression in cancer J Nucl Med 2013 54 5 776 784 10.2967/jnumed.112.111021 23487015 · DOI
  65. [72]van de Water JA Bagci-Onder T Agarwal AS Wakimoto H Roovers RC Zhu Y Therapeutic stem cells expressing variants of EGFR-specific nanobodies have antitumor effects Proc Natl Acad Sci USA 2012 109 41 16642 16647 10.1073/pnas.1202832109 23012408 PMC3478609 · DOI
  66. [73]Quader S Kataoka K Nanomaterial-enabled cancer therapy Mol Ther J Am Soc Gene Ther 2017 25 7 1501 1513 10.1016/j.ymthe.2017.04.026 PMC5498831 28532763 · DOI
  67. [74]Jain KK Nanomedicine: application of nanobiotechnology in medical practice Med Princ Pract. 2008 17 2 89 101 10.1159/000112961 18287791 · DOI
  68. [75]Uchegbu IF Siew A Nanomedicines and nanodiagnostics come of age J Pharm Sci 2013 102 2 305 310 10.1002/jps.23377 23175462 · DOI
  69. [76]Jain KK Advances in the field of nanooncology BMC Med. 2010 8 83 10.1186/1741-7015-8-83 21144040 PMC3018446 · DOI
  70. [78]Jain KK Nanodiagnostics: application of nanotechnology in molecular diagnostics Expert Rev Mol Diagn 2003 3 2 153 161 10.1586/14737159.3.2.153 12647993 · DOI
  71. [79]Fernandes C Suares D Yergeri MC Tumor microenvironment targeted nanotherapy Front Pharmacol 2018 9 1230 10.3389/fphar.2018.01230 30429787 PMC6220447 · DOI
  72. [80]Aslan B Ozpolat B Sood AK Lopez-Berestein G Nanotechnology in cancer therapy J Drug Target. 2013 21 10 904 913 10.3109/1061186X.2013.837469 24079419 PMC4057038 · DOI
  73. [81]Jain KK Recent advances in nanooncology Technol Cancer Res Treat 2008 7 1 1 13 10.1177/153303460800700101 18198919 · DOI
  74. [82]Jain KK Nanobiotechnology and personalized medicine Prog Mol Biol Transl Sci. 2011 104 325 354 10.1016/B978-0-12-416020-0.00008-5 22093223 · DOI
  75. [83]Wang M Thanou M Targeting nanoparticles to cancer Pharmacol Res. 2010 62 2 90 99 10.1016/j.phrs.2010.03.005 20380880 · DOI
  76. [84]Hua S de Matos MBC Metselaar JM Storm G Current trends and challenges in the clinical translation of nanoparticulate nanomedicines: pathways for translational development and commercialization Front Pharmacol 2018 9 790 10.3389/fphar.2018.00790 30065653 PMC6056679 · DOI
  77. [85]Sanna V Pala N Sechi M Targeted therapy using nanotechnology: focus on cancer Int J Nanomed. 2014 9 467 483 10.2147/IJN.S36654 PMC3896284 24531078 · DOI
  78. [86]Kim BY Rutka JT Chan WC Nanomedicine N Engl J Med. 2010 363 25 2434 2443 10.1056/NEJMra0912273 21158659 · DOI
  79. [87]Yoon JW Jiang W Rutka JT Huang Y Kim BYS Perspectives of nanotechnology in the management of gliomas Prog Neurol Surg. 2018 32 196 210 10.1159/000469691 29990985 · DOI
  80. [88]Arezumand R Alibakhshi A Ranjbari J Ramazani A Muyldermans S Nanobodies as novel agents for targeting angiogenesis in solid cancers Front Immunol. 2017 8 1746 10.3389/fimmu.2017.01746 29276515 PMC5727022 · DOI
  81. [89]Behdani M Zeinali S Khanahmad H Karimipour M Asadzadeh N Azadmanesh K Generation and characterization of a functional nanobody against the vascular endothelial growth factor receptor-2; angiogenesis cell receptor Mol Immunol. 2012 50 1–2 35 41 10.1016/j.molimm.2011.11.013 22208996 · DOI
  82. [90]Vosjan MJ Vercammen J Kolkman JA Stigter-van Walsum M Revets H van Dongen GA Nanobodies targeting the hepatocyte growth factor: potential new drugs for molecular cancer therapy Mol Cancer Ther. 2012 11 4 1017 1025 10.1158/1535-7163.MCT-11-0891 22319202 · DOI
  83. [91]Rissiek B Koch-Nolte F Magnus T Nanobodies as modulators of inflammation: potential applications for acute brain injury Front Cell Neurosci. 2014 8 344 10.3389/fncel.2014.00344 25374510 PMC4204521 · DOI
  84. [92]Ebrahimizadeh W Mousavi Gargari SL Javidan Z Rajabibazl M Production of novel VHH nanobody inhibiting angiogenesis by targeting binding site of VEGF Appl Biochem Biotechnol. 2015 176 7 1985 1995 10.1007/s12010-015-1695-y 26054617 · DOI
  85. [93]Oliveira S Schiffelers RM van der Veeken J van der Meel R Vongpromek R van Bergen En Henegouwen PM Downregulation of EGFR by a novel multivalent nanobody-liposome platform J Controll Release 2010 145 2 165 175 10.1016/j.jconrel.2010.03.020 20362020 · DOI
  86. [94]Talelli M Rijcken CJ Oliveira S van der Meel R van Bergen En Henegouwen PM Lammers T Nanobody-shell functionalized thermosensitive core-crosslinked polymeric micelles for active drug targeting J Controll Release 2011 151 2 183 192 10.1016/j.jconrel.2011.01.015 21262289 · DOI
  87. [95]Altintas I Heukers R van der Meel R Lacombe M Amidi M van Bergen En Henegouwen PM Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells J Controll Release. 2013 165 2 110 118 10.1016/j.jconrel.2012.11.007 23159529 · DOI
  88. [96]Mima T Nishimoto N Clinical value of blocking IL-6 receptor Curr Opin Rheumatol. 2009 21 3 224 230 10.1097/BOR.0b013e3283295fec 19365268 · DOI
  89. [97]Roovers RC Vosjan MJ Laeremans T el Khoulati R de Bruin RC Ferguson KM A biparatopic anti-EGFR nanobody efficiently inhibits solid tumour growth Int J Cancer 2011 129 8 2013 2024 10.1002/ijc.26145 21520037 PMC4197845 · DOI
  90. [98]Scully M Cataland SR Peyvandi F Coppo P Knobl P Kremer Hovinga JA Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura N Engl J Med. 2019 380 4 335 346 10.1056/NEJMoa1806311 30625070 · DOI
  91. [99]Xu X Vugmeyster Y Challenges and opportunities in absorption, distribution, metabolism, and excretion studies of therapeutic biologics AAPS J. 2012 14 4 781 791 10.1208/s12248-012-9388-8 22864668 PMC3475845 · DOI
  92. [100]Huehls AM Coupet TA Sentman CL Bispecific T-cell engagers for cancer immunotherapy Immunol Cell Biol. 2015 93 3 290 296 10.1038/icb.2014.93 25367186 PMC4445461 · DOI
  93. [101]Xing J Lin L Li J Liu J Zhou C Pan H BiHC, a T-cell-engaging bispecific recombinant antibody, has potent cytotoxic activity against Her2 tumor cells Transl Oncol. 2017 10 5 780 785 10.1016/j.tranon.2017.07.003 28797938 PMC5548338 · DOI
  94. [102]Lin L Li L Zhou C Li J Liu J Shu R A HER2 bispecific antibody can be efficiently expressed in Escherichia coli with potent cytotoxicity Oncol Lett. 2018 16 1 1259 1266 10.3892/ol.2018.8698 29963199 PMC6019972 · DOI
  95. [103]Molgaard K Harwood SL Compte M Merino N Bonet J Alvarez-Cienfuegos A Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies Cancer Immunol Immunother CII. 2018 67 8 1251 1260 10.1007/s00262-018-2181-5 29869168 PMC11028287 · DOI
  96. [104]Iri-Sofla FJ Rahbarizadeh F Ahmadvand D Rasaee MJ Nanobody-based chimeric receptor gene integration in Jurkat cells mediated by phiC31 integrase Exp Cell Res 2011 317 18 2630 2641 10.1016/j.yexcr.2011.08.015 21906589 · DOI
  97. [105]Albert S Arndt C Feldmann A Bergmann R Bachmann D Koristka S A novel nanobody-based target module for retargeting of T lymphocytes to EGFR-expressing cancer cells via the modular UniCAR platform Oncoimmunology. 2017 6 4 e1287246 10.1080/2162402X.2017.1287246 28507794 PMC5414885 · DOI
  98. [106]Steeland S Vandenbroucke RE Libert C Nanobodies as therapeutics: big opportunities for small antibodies Drug Discov Today. 2016 21 7 1076 1113 10.1016/j.drudis.2016.04.003 27080147 · DOI
  99. [107]van der Meel R Oliveira S Altintas I Haselberg R van der Veeken J Roovers RC Tumor-targeted Nanobullets: Anti-EGFR nanobody-liposomes loaded with anti-IGF-1R kinase inhibitor for cancer treatment J Controll Release 2012 159 2 281 289 10.1016/j.jconrel.2011.12.027 22227023 · DOI
  100. [108]Talelli M Iman M Varkouhi AK Rijcken CJ Schiffelers RM Etrych T Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin Biomaterials. 2010 31 30 7797 7804 10.1016/j.biomaterials.2010.07.005 20673684 · DOI
  101. [109]Moulder S Hortobagyi GN Advances in the treatment of breast cancer Clin Pharmacol Ther 2008 83 1 26 36 10.1038/sj.clpt.6100449 18091763 · DOI
  102. [110]Pruszynski M Koumarianou E Vaidyanathan G Revets H Devoogdt N Lahoutte T Targeting breast carcinoma with radioiodinated anti-HER2 nanobody Nucl Med Biol. 2013 40 1 52 59 10.1016/j.nucmedbio.2012.08.008 23159171 PMC3551612 · DOI
  103. [111]Van Heeke G Allosery K De Brabandere V De Smedt T Detalle L de Fougerolles A Nanobodies(R) as inhaled biotherapeutics for lung diseases Pharmacol Ther. 2017 169 47 56 10.1016/j.pharmthera.2016.06.012 27373507 · DOI
  104. [112]Hacha J Tomlinson K Maertens L Paulissen G Rocks N Foidart JM Nebulized anti-IL-13 monoclonal antibody Fab’ fragment reduces allergen-induced asthma Am J Respir Cell Mol Biol. 2012 47 5 709 717 10.1165/rcmb.2012-0031OC 22904197 · DOI
  105. [113]Maillet A Guilleminault L Lemarie E Lerondel S Azzopardi N Montharu J The airways, a novel route for delivering monoclonal antibodies to treat lung tumors Pharm Res. 2011 28 9 2147 2156 10.1007/s11095-011-0442-5 21491145 · DOI
  106. [114]Detalle L Stohr T Palomo C Piedra PA Gilbert BE Mas V Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection Antimicrob Agents Chemother. 2016 60 1 6 13 10.1128/AAC.01802-15 26438495 PMC4704182 · DOI
  107. [115]Wang SM He X Li N Yu F Hu Y Wang LS A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting Int J Nanomed 2015 10 2857 2869 10.2147/IJN.S77268 PMC4403696 25926731 · DOI
  108. [117]Shilo M Motiei M Hana P Popovtzer R Transport of nanoparticles through the blood–brain barrier for imaging and therapeutic applications Nanoscale. 2014 6 4 2146 2152 10.1039/c3nr04878k 24362586 · DOI
  109. [119]Eugenin EA Clements JE Zink MC Berman JW Human immunodeficiency virus infection of human astrocytes disrupts blood–brain barrier integrity by a gap junction-dependent mechanism J Neurosci 2011 31 26 9456 9465 10.1523/JNEUROSCI.1460-11.2011 21715610 PMC3132881 · DOI
  110. [122]Stanimirovic DB Sandhu JK Costain WJ Emerging technologies for delivery of biotherapeutics and gene therapy across the blood–brain barrier BioDrugs. 2018 32 6 547 559 10.1007/s40259-018-0309-y 30306341 PMC6290705 · DOI
  111. [123]Paterson J Webster CI Exploiting transferrin receptor for delivering drugs across the blood–brain barrier Drug Discov Today Technol 2016 20 49 52 10.1016/j.ddtec.2016.07.009 27986223 · DOI · Paper page
  112. [125]Niewoehner J Bohrmann B Collin L Urich E Sade H Maier P Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle Neuron. 2014 81 1 49 60 10.1016/j.neuron.2013.10.061 24411731 · DOI · Paper page
  113. [126]Pardridge WM Buciak JL Friden PM Selective transport of an anti-transferrin receptor antibody through the blood–brain barrier in vivo J Pharmacol Exp Ther 1991 259 1 66 70 1920136
  114. [127]Sade H Baumgartner C Hugenmatter A Moessner E Freskgard PO Niewoehner J A human blood–brain barrier transcytosis assay reveals antibody transcytosis influenced by pH-dependent receptor binding PLoS One. 2014 9 4 e96340 10.1371/journal.pone.0096340 24788759 PMC4005765 · DOI
  115. [128]Farrington GK Caram-Salas N Haqqani AS Brunette E Eldredge J Pepinsky B A novel platform for engineering blood–brain barrier-crossing bispecific biologics FASEB J 2014 28 11 4764 4778 10.1096/fj.14-253369 25070367 · DOI
  116. [129]Muruganandam A Tanha J Narang S Stanimirovic D Selection of phage-displayed llama single-domain antibodies that transmigrate across human blood-brain barrier endothelium FASEB J 2002 16 2 240 242 10.1096/fj.01-0343fje 11772942 · DOI
  117. [130]Tanha J Muruganandam A Stanimirovic D Phage display technology for identifying specific antigens on brain endothelial cells Methods Mol Med. 2003 89 435 449 10.1385/1-59259-419-0:435 12958438 · DOI
  118. [131]Abulrob A Sprong H Van Bergen en Henegouwen P Stanimirovic D The blood–brain barrier transmigrating single domain antibody: mechanisms of transport and antigenic epitopes in human brain endothelial cells J Neurochem. 2005 95 4 1201 1214 10.1111/j.1471-4159.2005.03463.x 16271053 · DOI
  119. [132]Haqqani AS Delaney CE Brunette E Baumann E Farrington GK Sisk W Endosomal trafficking regulates receptor-mediated transcytosis of antibodies across the blood–brain barrier J Cereb Blood Flow Metab 2018 38 4 727 740 10.1177/0271678X17740031 29140158 PMC5888858 · DOI
  120. [133]Suffredini G East JE Levy LM New applications of nanotechnology for neuroimaging AJNR Am J Neuroradiol. 2014 35 7 1246 1253 10.3174/ajnr.A3543 23538408 PMC7966599 · DOI
  121. [134]Li T Bourgeois JP Celli S Glacial F Le Sourd AM Mecheri S Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood–brain barrier and specifically recognize astrocytes: application to brain imaging FASEB J 2012 26 10 3969 3979 10.1096/fj.11-201384 22730440 · DOI
  122. [135]Rutgers KS Nabuurs RJ van den Berg SA Schenk GJ Rotman M Verrips CT Transmigration of beta amyloid specific heavy chain antibody fragments across the in vitro blood–brain barrier Neuroscience. 2011 190 37 42 10.1016/j.neuroscience.2011.05.076 21683126 · DOI
  123. [136]Caljon G Caveliers V Lahoutte T Stijlemans B Ghassabeh GH Van Den Abbeele J Using microdialysis to analyse the passage of monovalent nanobodies through the blood–brain barrier Br J Pharm. 2012 165 7 2341 2353 10.1111/j.1476-5381.2011.01723.x PMC3413867 22013955 · DOI
  124. [137]Roovers RC Laeremans T Huang L De Taeye S Verkleij AJ Revets H Efficient inhibition of EGFR signaling and of tumour growth by antagonistic anti-EFGR nanobodies Cancer Immunol Immunother CII. 2007 56 3 303 317 10.1007/s00262-006-0180-4 16738850 PMC11030579 · DOI
  125. [138]Hulstein JJ de Groot PG Silence K Veyradier A Fijnheer R Lenting PJ A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B Blood. 2005 106 9 3035 3042 10.1182/blood-2005-03-1153 16014562 · DOI
  126. [139]Bhoopalan SV Hankins J George J Ryder A Onder AM Puri L Use of caplacizumab in a child with refractory thrombotic thrombocytopenic purpura Pediatr Blood Cancer. 2019 66 7 e27737 10.1002/pbc.27737 30924605 · DOI
  127. [140]Kaczmarek V Holle J Astudillo R Kempf C Bufler P Muller D Caplacizumab for relapsing thrombotic thrombocytopenic purpura Pediatr Nephrol. 2019 10.1007/s00467-019-04281-z 31177334 · DOI
  128. [141]Peyvandi F Callewaert F Caplacizumab for acquired thrombotic thrombocytopenic purpura N Engl J Med. 2016 374 25 2497 2498 10.1056/NEJMc1603180 27332911 · DOI
  129. [142]Peyvandi F Scully M Kremer Hovinga JA Cataland S Knobl P Wu H Caplacizumab for acquired thrombotic thrombocytopenic purpura N Engl J Med. 2016 374 6 511 522 10.1056/NEJMoa1505533 26863353 · DOI
  130. [143]Peyvandi F Scully M Kremer Hovinga JA Knobl P Cataland S De Beuf K Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura J Thromb Haemost JTH. 2017 15 7 1448 1452 10.1111/jth.13716 28445600 · DOI
  131. [144]Kratz F Elsadek B Clinical impact of serum proteins on drug delivery J Controll Release. 2012 161 2 429 445 10.1016/j.jconrel.2011.11.028 22155554 · DOI
  132. [145]Van Roy M Ververken C Beirnaert E Hoefman S Kolkman J Vierboom M The preclinical pharmacology of the high affinity anti-IL-6R Nanobody(R) ALX-0061 supports its clinical development in rheumatoid arthritis Arthr Res Ther. 2015 17 135 10.1186/s13075-015-0651-0 25994180 PMC4476083 · DOI
  133. [146]Palomo C Mas V Detalle L Depla E Cano O Vazquez M Trivalency of a nanobody specific for the human respiratory syncytial virus fusion glycoprotein drastically enhances virus neutralization and impacts escape mutant selection Antimicrob Agents Chemother 2016 60 11 6498 6509 10.1128/AAC.00842-16 27550346 PMC5075053 · DOI
  134. [147]Svecova D Lubell MW Casset-Semanaz F Mackenzie H Grenningloh R Krueger JG A randomized, double-blind, placebo-controlled phase 1 study of multiple ascending doses of subcutaneous M1095, an anti-interleukin 17A/F nanobody, in moderate-to-severe psoriasis J Am Acad Dermatol. 2019 81 1 196 203 10.1016/j.jaad.2019.03.056 30926369 · DOI
  135. [148]De Munter S Ingels J Goetgeluk G Bonte S Pille M Weening K Nanobody based dual specific CARs Int J Mol Sci. 2018 19 2 1 10.3390/ijms19020403 PMC5855625 29385713 · DOI
  136. [149]Pereira J Ottevaere I Serruys B Dejonckheere E Bay-Jensen AC Siebuhr AS Pharmacokinetic and pharmacodynamic modelling of the novel anti-ADAMTS-5 nanobody M6495 using the neo-epitope ARGS as a biomarker Osteoarthr Cartil. 2018 26 S176 10.1016/j.joca.2018.02.381 · DOI
  137. [150]Siebuhr A Bay-Jensen AC Thudium CT Karsdal MA Serruys B Werkmann D The anti-ADAMTS-5 nanobody® M6495, protects against cartilage breakdown in cartilage and synovial joint tissue explant models Osteoarthr Cartil. 2018 26 S187 10.1016/j.joca.2018.02.402 · DOI
  138. [151]Sarker SA Jakel M Sultana S Alam NH Bardhan PK Chisti MJ Anti-rotavirus protein reduces stool output in infants with diarrhea: a randomized placebo-controlled trial Gastroenterology. 2013 145 4 740-8 e8 10.1053/j.gastro.2013.06.053 23831050 · DOI

Cited by

Sorted by citations

Authors
Jovčevska, I., & Muyldermans, S.
Affiliations
  • University of Ljubljana (SI)
  • Vrije Universiteit Brussel (BE)
Corresponding author
Muyldermans, Serge
ORCID
Venue
BioDrugs
Publisher
Springer Science and Business Media LLC
Published
2019-11-04
Volume
34
Issue
1
Pages
11-26
ISSN
  • 1172-7039 (ISSN-L)
  • 1173-8804
  • 1179-190X
DOI
10.1007/s40259-019-00392-z
PMC
PMC6985073
OpenAlex
W2983988502
Cited by
749
References
12
Citations by year
2026: 75 · 2025: 117 · 2024: 132 · 2023: 120 · 2022: 114 · 2021: 126 · 2020: 63 · 2019: 1 · 2012: 1
FWCI
11.40
Type
journal article
Language
en
Open access
Licence
Locations
  • BioDrugs (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Slovenian Research Agency (PO-1390, Z3-1869)
  • Interreg EC Project (2014-2020 Ref. No. 146)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Keywords
nanobodies, heavy-chain antibodies, camelid antibodies, nanomedicine, nanotherapy, cancer therapy, caplacizumab, thrombotic thrombocytopenic purpura, solid tumors, nanoparticle drug delivery
MeSH terms
Antibodies, Humans, Inflammation, Neoplasms, Single-Domain Antibodies

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review