Skip to main content

Camelid Single-Domain Antibodies for Targeting Cancer Nanotheranostics

  • Chapter
  • First Online:
Cancer Nanotheranostics

Abstract

Single-domain antibodies (VHHs), in particular those engineered from the variable heavy-chain fragment (VHH gene) found in Camelidae heavy-chain antibodies, are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs or targeting agents. The high stability of VHHs against high concentrations of organic solvents and extreme pHs and temperatures opens a wide range of applications for the detection of small molecules such as the development of more efficient methods of immobilization for biosensing purposes in addition to attachment sites in several immunotherapeutic constructs such as chimeric T cell therapy. VHHs, due to their unique 3D structure, have versatile abilities to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This chapter summarizes the applications and great potentials of VHHs as therapeutic tools or noninvasive in vivo molecular imaging agents. Moreover, the unique properties of VHHs are outlined like internalization, size, thermal and chemical stability, affinity, blood clearance, and labeling procedures. We highlight some already-reported therapeutic examples about VHHs being used for the treatment of several diseases such as cancer and several nanostructures which are used as molecular imaging or delivering tools.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Abedi-Gaballu, F., Dehghan, G., Ghaffari, M., Yekta, R., Abbaspour-Ravasjani, S., Baradaran, B., et al. (2018). PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy. Applied Materials Today, 12, 177–190.

    Article  PubMed  PubMed Central  Google Scholar 

  • Akhtari, J., Rezayat, S. M., Teymouri, M., Alavizadeh, S. H., Gheybi, F., Badiee, A., et al. (2016). Targeting, bio distributive and tumor growth inhibiting characterization of anti-HER2 affibody coupling to liposomal doxorubicin using BALB/c mice bearing TUBO tumors. International Journal of Pharmaceutics, 505(1–2), 89–95.

    Article  CAS  PubMed  Google Scholar 

  • Albert, S., Arndt, C., Feldmann, A., Bergmann, R., Bachmann, D., Koristka, S., et al. (2017). A novel nanobody-based target module for retargeting of T lymphocytes to EGFR-expressing cancer cells via the modular UniCAR platform. Oncoimmunology, 6(4), e1287246.

    Article  PubMed  PubMed Central  Google Scholar 

  • Albert, S., Arndt, C., Koristka, S., Berndt, N., Bergmann, R., Feldmann, A., et al. (2018). From mono-to bivalent: Improving theranostic properties of target modules for redirection of UniCAR T cells against EGFR-expressing tumor cells in vitro and in vivo. Oncotarget, 9(39), 25597.

    Article  PubMed  PubMed Central  Google Scholar 

  • An, N., Hou, Y. N., Zhang, Q. X., Li, T., Zhang, Q. L., Fang, C., et al. (2018). Anti-multiple myeloma activity of nanobody-based anti-CD38 chimeric antigen receptor T cells. Molecular Pharmaceutics, 15(10), 4577–4588.

    Article  CAS  PubMed  Google Scholar 

  • Bachmann, M. (2019). The UniCAR system: A modular CAR T cell approach to improve the safety of CAR T cells. Immunology Letters, 211, 13–22.

    Article  CAS  PubMed  Google Scholar 

  • Bachmann, D., Aliperta, R., Bergmann, R., Feldmann, A., Koristka, S., Arndt, C., et al. (2018). Retargeting of UniCAR T cells with an in vivo synthesized target module directed against CD19 positive tumor cells. Oncotarget, 9(7), 7487.

    Article  PubMed  Google Scholar 

  • Bala, G., Crauwels, M., Blykers, A., Remory, I., Marschall, A. L., Dübel, S., et al. (2019). Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for atherosclerosis–impact of radiochemistry on pharmacokinetics. Biological Chemistry, 400(3), 323–332.

    Article  CAS  PubMed  Google Scholar 

  • Bannas, P., Well, L., Lenz, A., Rissiek, B., Haag, F., Schmid, J., et al. (2014). In vivo near-infrared fluorescence targeting of T cells: Comparison of nanobodies and conventional monoclonal antibodies. Contrast Media & Molecular Imaging, 9(2), 135–142.

    Article  CAS  Google Scholar 

  • Barclay, J., Creswell, J., & León, J. (2018). Cancer immunotherapy and the PD-1/PD-L1 checkpoint pathway. Archivos Espanoles de Urologia, 71(4), 393–399.

    PubMed  Google Scholar 

  • Behdani, M., Zeinali, S., Karimipour, M., Khanahmad, H., Schoonooghe, S., Aslemarz, A., et al. (2013). Development of VEGFR2-specific nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth. New Biotechnology, 30(2), 205–209.

    Article  CAS  PubMed  Google Scholar 

  • Behr, T., Behe, M., & Wörmann, B. (2001). Trastuzumab and breast cancer. The New England Journal of Medicine, 345(13), 995–996.

    Article  CAS  PubMed  Google Scholar 

  • Beltrán-Gracia, E., López-Camacho, A., Higuera-Ciapara, I., Velázquez-Fernández, J. B., & Vallejo-Cardona, A. A. (2019). Nanomedicine review: Clinical developments in liposomal applications. Cancer Nanotechnology, 10(1), 11.

    Article  CAS  Google Scholar 

  • Böhmová, E., Machová, D., Pechar, M., Pola, R., Venclíková, K., Janoušková, O., et al. (2018). Cell-penetrating peptides: A useful tool for the delivery of various cargoes into cells. Physiological Research, 67, S267–SS79.

    Article  PubMed  Google Scholar 

  • Bridoux, J., Broos, K., Lecocq, Q., Debie, P., Martin, C., Ballet, S., et al. (2020). Anti-human PD-L1 nanobody for immuno-PET imaging: Validation of a conjugation strategy for clinical translation. Biomolecules, 10(10), 1388.

    Article  CAS  PubMed Central  Google Scholar 

  • Brown, L. F., Berse, B., Jackman, R. W., Tognazzi, K., Manseau, E. J., Senger, D. R., et al. (1993). Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Research, 53(19), 4727–4735.

    CAS  PubMed  Google Scholar 

  • Chabrol, E., Stojko, J., Nicolas, A., Botzanowski, T., Fould, B., Antoine, M., et al. (2020). VHH characterization. Recombinant VHHs: Production, characterization and affinity. Analytical Biochemistry, 589, 113491.

    Article  CAS  PubMed  Google Scholar 

  • Christiansen, J., & Rajasekaran, A. K. (2004). Biological impediments to monoclonal antibody–based cancer immunotherapy. Molecular Cancer Therapeutics, 3(11), 1493–1501.

    Article  CAS  PubMed  Google Scholar 

  • Cooke, C.-L. M., & Davidge, S. T. (2002). Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells. American Journal of Physiology-Cell Physiology, 282(2), C395–C402.

    Article  CAS  PubMed  Google Scholar 

  • D’Hollander, A., Jans, H., Velde, G. V., Verstraete, C., Massa, S., Devoogdt, N., et al. (2017). Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars. Biomaterials, 123, 15–23.

    Article  PubMed  CAS  Google Scholar 

  • D’Huyvetter, M., De Vos, J., Xavier, C., Pruszynski, M., Sterckx, Y. G., Massa, S., et al. (2017). 131I-labeled anti-HER2 camelid sdAb as a theranostic tool in cancer treatment. Clinical Cancer Research, 23(21), 6616–6628.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Meyer, T., Muyldermans, S., & Depicker, A. (2014). Nanobody-based products as research and diagnostic tools. Trends in Biotechnology, 32(5), 263–270.

    Article  PubMed  CAS  Google Scholar 

  • De Munter, S., Ingels, J., Goetgeluk, G., Bonte, S., Pille, M., Weening, K., et al. (2018). Nanobody based dual specific CARs. International Journal of Molecular Sciences, 19(2), 403.

    Article  PubMed Central  CAS  Google Scholar 

  • Deng, C., Xiong, J., Gu, X., Chen, X., Wu, S., Wang, Z., et al. (2017). Novel recombinant immunotoxin of EGFR specific nanobody fused with cucurmosin, construction and antitumor efficiency in vitro. Oncotarget, 8(24), 38568–38580.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dong, J., Huang, B., Jia, Z., Wang, B., Kankanamalage, S. G., Titong, A., et al. (2020). Development of multi-specific humanized llama antibodies blocking SARS-CoV-2/ACE2 interaction with high affinity and avidity. Emerging Microbes & Infections, 9(1), 1034–1036.

    Article  CAS  Google Scholar 

  • Drent, E., Groen, R. W., Noort, W. A., Themeli, M., van Bueren, J. J. L., Parren, P. W., et al. (2016). Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica, 101(5), 616–625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drent, E., Themeli, M., Poels, R., de Jong-Korlaar, R., Yuan, H., de Bruijn, J., et al. (2017). A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Molecular Therapy, 25(8), 1946–1958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eladl, E., Tremblay-LeMay, R., Rastgoo, N., Musani, R., Chen, W., Liu, A., et al. (2020). Role of CD47 in hematological malignancies. Journal of Hematology & Oncology, 13(1), 1–14.

    Article  Google Scholar 

  • Eloy, J. O., Petrilli, R., Trevizan, L. N. F., & Chorilli, M. (2017). Immunoliposomes: A review on functionalization strategies and targets for drug delivery. Colloids and Surfaces B: Biointerfaces, 159, 454–467.

    Article  CAS  PubMed  Google Scholar 

  • Emerich, D. F., Dean, R. L., Snodgrass, P., Lafreniere, D., Agostino, M., Wiens, T., et al. (2001). Bradykinin modulation of tumor vasculature: II. Activation of nitric oxide and phospholipase A2/prostaglandin signaling pathways synergistically modifies vascular physiology and morphology to enhance delivery of chemotherapeutic agents to tumors. Journal of Pharmacology and Experimental Therapeutics, 296(2), 632–641.

    CAS  Google Scholar 

  • Eroğlu, İ., & İbrahim, M. (2020). Liposome–ligand conjugates: A review on the current state of art. Journal of Drug Targeting, 28(3), 225–244.

    Article  PubMed  Google Scholar 

  • Fana, M., Gallien, J., Srinageshwar, B., Dunbar, G. L., & Rossignol, J. (2020). PAMAM dendrimer nanomolecules utilized as drug delivery systems for potential treatment of glioblastoma: A systematic review. International Journal of Nanomedicine, 15, 2789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang, T., Duarte, J. N., Ling, J., Li, Z., Guzman, J. S., & Ploegh, H. L. (2016). Structurally defined αMHC-II nanobody–drug conjugates: A therapeutic and imaging system for B-cell lymphoma. Angewandte Chemie International Edition, 55(7), 2416–2420.

    Article  CAS  PubMed  Google Scholar 

  • Farasat, A., Rahbarizadeh, F., Ahmadvand, D., & Yazdian, F. (2017). Optimization of an anti-HER2 nanobody expression using the Taguchi method. Preparative Biochemistry and Biotechnology, 47(8), 795–803.

    Article  CAS  PubMed  Google Scholar 

  • Farasat, A., Rahbarizadeh, F., Ahmadvand, D., Ranjbar, S., & Khoshtinat, N. S. (2019). Effective suppression of tumour cells by oligoclonal HER2-targeted delivery of liposomal doxorubicin. Journal of Liposome Research, 29(1), 53–65.

    Article  PubMed  Google Scholar 

  • Folkman, J. (2006). Angiogenesis. Annual Review of Medicine, 57(1), 1–18.

    Article  CAS  PubMed  Google Scholar 

  • Galluzzi, L., Humeau, J., Buqué, A., Zitvogel, L., & Kroemer, G. (2020). Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nature Reviews Clinical Oncology, 17(12), 725–741.

    Article  PubMed  Google Scholar 

  • Gee, M. S., Saunders, H. M., Lee, J. C., Sanzo, J. F., Jenkins, W. T., Evans, S. M., et al. (2001). Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations. Cancer Research, 61(7), 2974–2982.

    CAS  PubMed  Google Scholar 

  • Guillerey, C., Huntington, N. D., & Smyth, M. J. (2016). Targeting natural killer cells in cancer immunotherapy. Nature Immunology, 17(9), 1025–1036.

    Article  CAS  PubMed  Google Scholar 

  • Hajari Taheri, F., Hassani, M., Sharifzadeh, Z., Behdani, M., Arashkia, A., & Abolhassani, M. (2019). T cell engineered with a novel nanobody-based chimeric antigen receptor against VEGFR2 as a candidate for tumor immunotherapy. IUBMB Life, 71(9), 1259–1267.

    Article  CAS  PubMed  Google Scholar 

  • Hambach, J., Riecken, K., Cichutek, S., Schütze, K., Albrecht, B., Petry, K., et al. (2020). Targeting CD38-expressing multiple myeloma and Burkitt lymphoma cells in vitro with nanobody-based chimeric antigen receptors (Nb-CARs). Cell, 9(2), 321.

    Article  CAS  Google Scholar 

  • Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hammers, C., Songa, E. B., et al. (1993). Naturally occurring antibodies devoid of light chains. Nature, 363(6428), 446–448.

    Article  CAS  PubMed  Google Scholar 

  • Harmsen, M., & De Haard, H. (2007). Properties, production, and applications of camelid single-domain antibody fragments. Applied Microbiology and Biotechnology, 77(1), 13–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hassani, M., Hajari Taheri, F., Sharifzadeh, Z., Arashkia, A., Hadjati, J., van Weerden, W. M., et al. (2019). Construction of a chimeric antigen receptor bearing a nanobody against prostate a specific membrane antigen in prostate cancer. Journal of Cellular Biochemistry, 120(6), 10787–10795.

    Article  CAS  PubMed  Google Scholar 

  • Hatahet, F., Nguyen, V. D., Salo, K. E., & Ruddock, L. W. (2010). Disruption of reducing pathways is not essential for efficient disulfide bond formation in the cytoplasm of E. coli. Microbial Cell Factories, 9(1), 67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Havel, J. J., Chowell, D., & Chan, T. A. (2019). The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nature Reviews Cancer, 19(3), 133–150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henry, K. A., Hussack, G., Kumaran, J., Gilbert, M., MacKenzie, C. R., Sulea, T., et al. (2019). Role of the non-hypervariable FR3 D-E loop in single-domain antibody recognition of haptens and carbohydrates. Journal of Molecular Recognition, 32(11), e2805.

    Article  CAS  PubMed  Google Scholar 

  • Herrmann, J. (2020). Adverse cardiac effects of cancer therapies: Cardiotoxicity and arrhythmia. Nature Reviews Cardiology, 17(8), 474–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hervé-Aubert, K., David, S., Lautram, N., Passirani, C., Chourpa, I., Aubrey, N., et al. (2020). Targeted nanomedicine with anti-EGFR scFv for siRNA delivery into triple negative breast cancer cells. European Journal of Pharmaceutics and Biopharmaceutics, 157, 74–84.

    Article  PubMed  CAS  Google Scholar 

  • Hoyt, K., Umphrey, H., Lockhart, M., Robbin, M., & Forero-Torres, A. (2015). Ultrasound imaging of breast tumor perfusion and neovascular morphology. Ultrasound in Medicine & Biology, 41(9), 2292–2302.

    Article  Google Scholar 

  • Huang, H.-F., Zhu, H., Li, G.-H., Xie, Q., Yang, X.-T., Xu, X.-X., et al. (2019). Construction of anti-hPD-L1 HCAb Nb6 and in situ 124I labeling for noninvasive detection of PD-L1 expression in human bone sarcoma. Bioconjugate Chemistry, 30(10), 2614–2623.

    Article  CAS  PubMed  Google Scholar 

  • Huda, S., Alam, M. A., & Sharma, P. K. (2020). Smart nanocarriers-based drug delivery for cancer therapy: An innovative and developing strategy. Journal of Drug Delivery Science and Technology, 60, 102018.

    Article  CAS  Google Scholar 

  • Iezzi, M. E., Policastro, L., Werbajh, S., Podhajcer, O., & Canziani, G. A. (2018). Single-domain antibodies and the promise of modular targeting in cancer imaging and treatment. Frontiers in Immunology, 9, 273.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iqbal, U., Trojahn, U., Albaghdadi, H., Zhang, J., O’Connor-McCourt, M., Stanimirovic, D., et al. (2010). Kinetic analysis of novel mono-and multivalent VHH-fragments and their application for molecular imaging of brain tumours. British Journal of Pharmacology, 160(4), 1016–1028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iri-Sofla, F. J., Rahbarizadeh, F., Ahmadvand, D., & Rasaee, M. J. (2011). Nanobody-based chimeric receptor gene integration in Jurkat cells mediated by PhiC31 integrase. Experimental Cell Research, 317(18), 2630–2641.

    Article  CAS  PubMed  Google Scholar 

  • Jafari Iri Sofla, F., Rahbarizadeh, F., Ahmadvand, D., Nomani, A., & Vernet, E. (2019). Anti–HER2 single domain antibody-conjugated dendrimers for targeted delivery of truncated-bid transgene to breast cancer cells. Journal of Bioactive and Compatible Polymers, 34(1), 39–57.

    Article  CAS  Google Scholar 

  • Jamnani, F. R., Rahbarizadeh, F., Shokrgozar, M. A., Mahboudi, F., Ahmadvand, D., Sharifzadeh, Z., et al. (2014). T cells expressing VHH-directed oligoclonal chimeric HER2 antigen receptors: Towards tumor-directed oligoclonal T cell therapy. Biochimica et Biophysica Acta (BBA)-General Subjects, 1840(1), 378–386.

    Article  CAS  Google Scholar 

  • Jia, D., Yang, Y., Yuan, F., Fan, Q., Wang, F., Huang, Y., et al. (2020). Increasing the antitumor efficacy of doxorubicin liposomes with coupling an anti-EGFR affibody in EGFR-expressing tumor models. International Journal of Pharmaceutics, 586, 119541.

    Article  CAS  PubMed  Google Scholar 

  • Jureczek, J., Feldmann, A., Bergmann, R., Arndt, C., Berndt, N., Koristka, S., et al. (2020). Highly efficient targeting of EGFR-expressing tumor cells with UniCAR T cells via target modules based on Cetuximab®. OncoTargets and Therapy, 13, 5515–5527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalyane, D., Raval, N., Maheshwari, R., Tambe, V., Kalia, K., & Tekade, R. K. (2019). Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Materials Science and Engineering: C, 98, 1252–1276.

    Article  CAS  Google Scholar 

  • Kaplan, O., Zarubova, J., Mikulova, B., Filova, E., Bártová, J., Bačáková, L., et al. (2016). Enhanced mitogenic activity of recombinant human vascular endothelial growth factor VEGF121 expressed in E. coli origami B (DE3) with molecular chaperones. PLoS One, 11(10), e0163697.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Khaleghi, S., Rahbarizadeh, F., Ahmadvand, D., Rasaee, M. J., & Pognonec, P. (2012). A caspase 8-based suicide switch induces apoptosis in nanobody-directed chimeric receptor expressing T cells. International Journal of Hematology, 95(4), 434–444.

    Article  CAS  PubMed  Google Scholar 

  • Khaleghi, S., Rahbarizadeh, F., Ahmadvand, D., Malek, M., & Madaah Hosseini, H. R. (2016). The effect of superparamagnetic iron oxide nanoparticles surface engineering on relaxivity of magnetoliposome. Contrast Media & Molecular Imaging, 11(5), 340–349.

    Article  CAS  Google Scholar 

  • Khaleghi, S., Rahbarizadeh, F., Ahmadvand, D., & Hosseini, H. R. M. (2017). Anti-HER2 VHH targeted magnetoliposome for intelligent magnetic resonance imaging of breast cancer cells. Cellular and Molecular Bioengineering, 10(3), 263–272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kijanka, M. M., van Brussel, A. S., van der Wall, E., Mali, W. P., van Diest, P. J., van Bergen En Henegouwen, P. M., et al. (2016). Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization. EJNMMI Research, 6(1), 14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kirchhofer, A., Helma, J., Schmidthals, K., Frauer, C., Cui, S., Karcher, A., et al. (2010). Modulation of protein properties in living cells using nanobodies. Nature Structural & Molecular Biology, 17(1), 133.

    Article  CAS  Google Scholar 

  • Koning, G. A., Eggermont, A. M., Lindner, L. H., & ten Hagen, T. L. (2010). Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors. Pharmaceutical Research, 27(8), 1750–1754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubala, M. H., Kovtun, O., Alexandrov, K., & Collins, B. M. (2010). Structural and thermodynamic analysis of the GFP: GFP-nanobody complex. Protein Science, 19(12), 2389–2401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lassere, M. N. (2008). The Biomarker-Surrogacy Evaluation Schema: A review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints. Statistical Methods in Medical Research, 17(3), 303–340.

    Article  PubMed  Google Scholar 

  • Lecocq, Q., Zeven, K., De Vlaeminck, Y., Martens, S., Massa, S., Goyvaerts, C., et al. (2019). Noninvasive imaging of the immune checkpoint LAG-3 using nanobodies, from development to pre-clinical use. Biomolecules, 9(10), 548.

    Article  PubMed Central  CAS  Google Scholar 

  • Leemasawat, K., Phrommintikul, A., Chattipakorn, S. C., & Chattipakorn, N. (2020). Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients. Cellular and Molecular Life Sciences, 77(8), 1571–1589.

    Article  CAS  PubMed  Google Scholar 

  • Li, T., Bourgeois, J. P., Celli, S., Glacial, F., Le Sourd, A. M., Mecheri, S., et al. (2012). 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. The FASEB Journal, 26(10), 3969–3979.

    Article  CAS  PubMed  Google Scholar 

  • Li, J. Y., Perry, S. R., Muniz-Medina, V., Wang, X., Wetzel, L. K., Rebelatto, M. C., et al. (2016). A biparatopic HER2-targeting antibody-drug conjugate induces tumor regression in primary models refractory to or ineligible for HER2-targeted therapy. Cancer Cell, 29(1), 117–129.

    Article  CAS  PubMed  Google Scholar 

  • Li, J., Liang, H., Liu, J., & Wang, Z. (2018). Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy. International Journal of Pharmaceutics, 546(1–2), 215–225.

    Article  CAS  PubMed  Google Scholar 

  • Liu, S., Pan, J., Liu, J., Ma, Y., Qiu, F., Mei, L., et al. (2018). Dynamically PEGylated and borate-coordination-polymer-coated polydopamine nanoparticles for synergetic tumor-targeted, chemo-photothermal combination therapy. Small, 14(13), 1703968.

    Article  CAS  Google Scholar 

  • Lobstein, J., Emrich, C. A., Jeans, C., Faulkner, M., Riggs, P., & Berkmen, M. (2012). SHuffle, a novel Escherichia coli protein expression strain capable of correctly folding disulfide bonded proteins in its cytoplasm. Microbial Cell Factories, 11(1), 753.

    Article  CAS  Google Scholar 

  • Loureiro, L., Feldmann, A., Bergmann, R., Koristka, S., Berndt, N., Arndt, C., et al. (2018). Development of a novel target module redirecting UniCAR T cells to Sialyl Tn-expressing tumor cells. Blood Cancer Journal, 8(9), 1–6.

    Article  CAS  Google Scholar 

  • Lugano, R., Ramachandran, M., & Dimberg, A. (2020). Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cellular and Molecular Life Sciences, 77(9), 1745–1770.

    Article  CAS  PubMed  Google Scholar 

  • Luong, D., Kesharwani, P., Deshmukh, R., Amin, M. C. I. M., Gupta, U., Greish, K., et al. (2016). PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery. Acta Biomaterialia, 43, 14–29.

    Article  CAS  PubMed  Google Scholar 

  • Manglik, A., Kobilka, B. K., & Steyaert, J. (2017). Nanobodies to study G protein–coupled receptor structure and function. Annual Review of Pharmacology and Toxicology, 57, 19–37.

    Article  CAS  PubMed  Google Scholar 

  • Marcucci, F., Bellone, M., Rumio, C., & Corti, A. (2013). Approaches to improve tumor accumulation and interactions between monoclonal antibodies and immune cells. MAbs, 5(1), 34–46. Taylor & Francis.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mikkilineni, L., & Kochenderfer, J. N. (2021). CAR T cell therapies for patients with multiple myeloma. Nature Reviews Clinical Oncology, 18(2), 71–84.

    Article  CAS  PubMed  Google Scholar 

  • Mir, M. A., Mehraj, U., Sheikh, B. A., & Hamdani, S. S. (2020). Nanobodies: The “magic bullets” in therapeutics, drug delivery and diagnostics. Human Antibodies, 28(1), 29–51.

    Article  CAS  PubMed  Google Scholar 

  • Muyldermans, S. (2020). A guide to: Generation and design of nanobodies. The FEBS Journal. https://doi.org/10.1111/febs.15515

  • Myers, J. A., & Miller, J. S. (2021). Exploring the NK cell platform for cancer immunotherapy. Nature Reviews Clinical Oncology, 18(2), 85–100.

    Article  PubMed  Google Scholar 

  • Ng, Q.-S., Goh, V., Milner, J., Stratford, M. R., Folkes, L. K., Tozer, G. M., et al. (2007). Effect of nitric-oxide synthesis on tumour blood volume and vascular activity: A phase I study. The Lancet Oncology, 8(2), 111–118.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen, V. D., Hatahet, F., Salo, K. E., Enlund, E., Zhang, C., & Ruddock, L. W. (2011). Pre-expression of a sulfhydryl oxidase significantly increases the yields of eukaryotic disulfide bond containing proteins expressed in the cytoplasm of E. coli. Microbial Cell Factories, 10(1), 1–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikkhoi, S. K., Rahbarizadeh, F., & Ahmadvand, D. (2017). Oligo-clonal nanobodies as an innovative targeting agent for cancer therapy: New biology and novel targeting systems. Protein Expression and Purification, 129, 115–121.

    Article  CAS  PubMed  Google Scholar 

  • Nikkhoi, S. K., Rahbarizadeh, F., Ahmadvand, D., & Moghimi, S. M. (2018). Multivalent targeting and killing of HER2 overexpressing breast carcinoma cells with methotrexate-encapsulated tetra-specific non-overlapping variable domain heavy chain anti-HER2 antibody-PEG-liposomes: In vitro proof-of-concept. European Journal of Pharmaceutical Sciences, 122, 42–50.

    Article  CAS  Google Scholar 

  • Oliveira, S., Heukers, R., Sornkom, J., Kok, R. J., & van Bergen En Henegouwen, P. M. (2013). Targeting tumors with nanobodies for cancer imaging and therapy. Journal of Controlled Release, 172(3), 607–617.

    Article  CAS  PubMed  Google Scholar 

  • Osman, G., Rodriguez, J., Chan, S. Y., Chisholm, J., Duncan, G., Kim, N., et al. (2018). PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy. Journal of Controlled Release, 285, 35–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Padegimas, A., Clasen, S., & Ky, B. (2020). Cardioprotective strategies to prevent breast cancer therapy-induced cardiotoxicity. Trends in Cardiovascular Medicine, 30(1), 22–28.

    Article  CAS  PubMed  Google Scholar 

  • Pannuzzo, M., Esposito, S., Wu, L.-P., Key, J., Aryal, S., Celia, C., et al. (2020). Overcoming nanoparticle-mediated complement activation by surface PEG-pairing. Nano Letters, 20(6), 4312–4321.

    Article  CAS  PubMed  Google Scholar 

  • Patel, V. (2020). Liposome: A novel carrier for targeting drug delivery system. Asian Journal of Pharmaceutical Research and Development, 8(4), 67–76.

    CAS  Google Scholar 

  • Prasad, R., Jain, N. K., Yadav, A. S., Chauhan, D. S., Devrukhkar, J., Kumawat, M. K., et al. (2020). Liposomal nanotheranostics for multimode targeted in vivo bioimaging and near-infrared light mediated cancer therapy. Communications Biology, 3(1), 1–14.

    Article  Google Scholar 

  • Qin, L.-J., Gu, Y.-T., Zhang, H., & Xue, Y.-X. (2009). Bradykinin-induced blood–tumor barrier opening is mediated by tumor necrosis factor-α. Neuroscience Letters, 450(2), 172–175.

    Article  CAS  PubMed  Google Scholar 

  • Rajabzadeh, A., Hamidieh, A. A., & Rahbarizadeh, F. (2018). Cytotoxic function of chimeric antigen receptor (CAR) T cells redirected by anti-Muci nanobody. Biology of Blood and Marrow Transplantation, 24(3), S474.

    Article  Google Scholar 

  • Rajabzadeh, A., Rahbarizadeh, F., Ahmadvand, D., Kabir, S. M., & Hamidieh, A. A. (2021). A VHH-based anti-MUC1 chimeric antigen receptor for specific retargeting of human primary T cells to MUC1-positive cancer cells. Cell Journal, 22(4), 502.

    PubMed  Google Scholar 

  • Saqafi, B., & Rahbarizadeh, F. (2018). Specific targeting of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells by polyethylene glycol-grafted polyethyleneimine modified with anti-HER2 single-domain antibody. Journal of Bioactive and Compatible Polymers, 33(1), 17–37.

    Article  CAS  Google Scholar 

  • Saqafi, B., & Rahbarizadeh, F. (2019). Polyethyleneimine-polyethylene glycol copolymer targeted by anti-HER2 nanobody for specific delivery of transcriptionally targeted tBid containing construct. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 501–511.

    Article  CAS  PubMed  Google Scholar 

  • Sercombe, L., Veerati, T., Moheimani, F., Wu, S. Y., Sood, A. K., & Hua, S. (2015). Advances and challenges of liposome assisted drug delivery. Frontiers in Pharmacology, 6, 286.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shimasaki, N., Jain, A., & Campana, D. (2020). NK cells for cancer immunotherapy. Nature Reviews Drug Discovery, 19(3), 200–218.

    Article  CAS  PubMed  Google Scholar 

  • Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., et al. (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. The New England Journal of Medicine, 344(11), 783–792.

    Article  CAS  PubMed  Google Scholar 

  • Song, C. W., Lokshina, A., Rhee, J. G., Patten, M., & Levitt, S. H. (1984). Implication of blood flow in hyperthermic treatment of tumors. IEEE Transactions on Biomedical Engineering, 1, 9–16.

    Article  Google Scholar 

  • Sonveaux, P., Kaz, A. M., Snyder, S. A., Richardson, R. A., Cárdenas-Navia, L. I., Braun, R. D., et al. (2005). Oxygen regulation of tumor perfusion by S-nitrosohemoglobin reveals a pressor activity of nitric oxide. Circulation Research, 96(10), 1119–1126.

    Article  CAS  PubMed  Google Scholar 

  • Sun, Y., Kang, C., Yao, Z., Liu, F., & Zhou, Y. (2016). Peptide-based ligand for active delivery of liposomal doxorubicin. Nano Life, 6(03n04), 1642004.

    Article  CAS  Google Scholar 

  • Tang, J., Li, J., Zhu, X., Yu, Y., Chen, D., Yuan, L., et al. (2016). Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells. Oncotarget, 7(23), 34070.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thueng-In, K., Thanongsaksrikul, J., Srimanote, P., Bangphoomi, K., Poungpair, O., Maneewatch, S., et al. (2012). Cell penetrable humanized-VH/VHH that inhibit RNA dependent RNA polymerase (NS5B) of HCV. PLoS One, 7(11), e49254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thurber, G. M., Schmidt, M. M., & Wittrup, K. D. (2008). Antibody tumor penetration: Transport opposed by systemic and antigen-mediated clearance. Advanced Drug Delivery Reviews, 60(12), 1421–1434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tian, B., Wong, W. Y., Hegmann, E., Gaspar, K., Kumar, P., & Chao, H. (2015). Production and characterization of a camelid single domain antibody–urease enzyme conjugate for the treatment of cancer. Bioconjugate Chemistry, 26(6), 1144–1155.

    Article  CAS  PubMed  Google Scholar 

  • Tian, B., Wong, W. Y., Uger, M. D., Wisniewski, P., & Chao, H. (2017). Development and characterization of a camelid single domain antibody–urease conjugate that targets vascular endothelial growth factor receptor 2. Frontiers in Immunology, 8, 956.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Verhelle, A., Van Overbeke, W., Peleman, C., De Smet, R., Zwaenepoel, O., Lahoutte, T., et al. (2016). Non-invasive imaging of amyloid deposits in a mouse model of AGel using 99m Tc-modified nanobodies and SPECT/CT. Molecular Imaging and Biology, 18(6), 887–897.

    Article  CAS  PubMed  Google Scholar 

  • Vincke, C., Loris, R., Saerens, D., Martinez-Rodriguez, S., Muyldermans, S., & Conrath, K. (2009). General strategy to humanize a camelid single-domain antibody and identification of a universal humanized nanobody scaffold. Journal of Biological Chemistry, 284(5), 3273–3284.

    Article  CAS  Google Scholar 

  • Vong, L. B., & Nagasaki, Y. (2020). Nitric oxide nano-delivery systems for cancer therapeutics: Advances and challenges. Antioxidants, 9(9), 791.

    Article  CAS  PubMed Central  Google Scholar 

  • Wagner, H. N., Wiseman, G. A., Marcus, C. S., Nabi, H. A., Nagle, C. E., Fink-Bennett, D. M., et al. (2002). Administration guidelines for radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-labeled anti-CD20 monoclonal antibody. Journal of Nuclear Medicine, 43(2), 267–272.

    CAS  PubMed  Google Scholar 

  • Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020). A guide to cancer immunotherapy: From T cell basic science to clinical practice. Nature Reviews Immunology, 20(11), 651–668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, J., Wu, N., Cham, M. D., & Song, Y. (2009). Tumor response in patients with advanced non–small cell lung cancer: Perfusion CT evaluation of chemotherapy and radiation therapy. American Journal of Roentgenology, 193(4), 1090–1096.

    Article  PubMed  Google Scholar 

  • Wang, Y., Fan, Z., Shao, L., Kong, X., Hou, X., Tian, D., et al. (2016). Nanobody-derived nanobiotechnology tool kits for diverse biomedical and biotechnology applications. International Journal of Nanomedicine, 11, 3287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, T., Liu, J., Liu, M., Liu, S., Zhao, S., Tian, R., et al. (2019). A nanobody-conjugated DNA nanoplatform for targeted platinum-drug delivery. Angewandte Chemie International Edition, 58(40), 14224–14228.

    Article  CAS  PubMed  Google Scholar 

  • Xiao, T., Li, D., Shi, X., & Shen, M. (2020). PAMAM dendrimer-based nanodevices for nuclear medicine applications. Macromolecular Bioscience, 20(2), 1900282.

    Article  CAS  Google Scholar 

  • Xie, Y. J., Dougan, M., Jailkhani, N., Ingram, J., Fang, T., Kummer, L., et al. (2019). Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proceedings of the National Academy of Sciences, 116(16), 7624–7631.

    Article  CAS  Google Scholar 

  • Xie, Y. J., Dougan, M., Ingram, J. R., Pishesha, N., Fang, T., Momin, N., et al. (2020). Improved antitumor efficacy of chimeric antigen receptor T cells that secrete single-domain antibody fragments. Cancer Immunology Research, 8(4), 518–529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, G., Yu, X., Zhang, J., Sheng, Y., Liu, G., Tao, W., et al. (2016). Robust aptamer–polydopamine-functionalized M-PLGA–TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy. International Journal of Nanomedicine, 11, 2953.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, Y., Wu, H., Huang, J., Qian, W., Martinson, D. E., Ji, B., et al. (2020). Probing and enhancing ligand-mediated active targeting of tumors using sub-5 nm ultrafine iron oxide nanoparticles. Theranostics, 10(6), 2479–2494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, J., Zhou, M., & Li, C. (2016). Synthetic nanoparticles for delivery of radioisotopes and radiosensitizers in cancer therapy. Cancer Nanotechnology, 7(1), 1–23.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fatemeh Rahbarizadeh PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Khaleghi, S., Khoshtinat Nikkhoi, S., Rahbarizadeh, F. (2021). Camelid Single-Domain Antibodies for Targeting Cancer Nanotheranostics. In: Saravanan, M., Barabadi, H. (eds) Cancer Nanotheranostics. Nanotechnology in the Life Sciences. Springer, Cham. https://doi.org/10.1007/978-3-030-74330-7_4

Download citation

Publish with us

Policies and ethics