Single Domain Antibodies: Tools for the Future?

The Advantages of Single Domain Antibodies

Conventional antibodies such as monoclonal (mAb) and polyclonal (pAb) antibodies have been at the forefront of biomedical research, use in diagnostic assays therapies against cancer, immune disorders, and infectious diseases. The market for antibodies is growing significantly as the need for these tools is ever-increasing to keep up with the constant battle between diseases and human health.

Disadvantages of Conventional Antibodies

Although conventional antibodies serve as the foundation for highly successful research, diagnostic and therapeutic tools, they do have their disadvantages such as stability over a narrow pH and temperature range and may not be able to access particular active sites on proteins.

These disadvantages might not hinder your research results, but a smaller-sized single domain antibody can increase therapeutic efficacy. A study from the Annals of Medicine, about the challenges in monoclonal antibody-based therapies, pointed out how the current manufacturing and purification processes of monoclonal antibodies cause limitations in the production capacity of therapeutic antibodies, which leads to an increase in cost (1). In a study by Vanlandschoot et al. (2), the advantages of sdAbs were reviewed in relation to their possible therapeutic applications against various viral diseases such as human immunodeficiency virus-1 (HIV-1), influenza A virus, reparatory syncytial virus (RSV), are discussed. View here. Such studies culminated in the first FDA-approved sdAb against von Willebrand factor to treat the blood disease Acquired Thrombotic Thrombocytopenia (3).

How Single Domain Antibodies Can Help

Single domain antibodies from camelid, aim to be the cutting-edge tool for antibody research in cellular mechanisms, cancer, and infectious diseases. These sdAbs lack light chains and are smaller and more stable than conventional antibodies yet they possess a fully functional antigen-binding capacity. Due to their size (approximately 15 kDa) and their longer and structurally unique Complementarity Determining Region 3 (CDR3 region), a single domain antibody is adept at reaching otherwise inaccessible unique conformational features on a target that may play a crucial role in the molecular mechanisms of disease.

single domain antibody

Conventional antibody vs. Single domain antibody

Features and Benefits of Single Domain Antibodies

Here are ways sdAbs can help excel your research:

  • Smallest functional antibody unit at ~15kDa; conventional antibody is ~150kDa
  • Enhanced tissue penetration, can cross the blood-brain barrier
  • Unique binding capacity to small cavities or clefts
  • High affinity and specificity
  • Highly stable at room temperature and under extreme temperatures and pH
  • High solubility, great imaging agents due to rapid clearance in vivo
  • Cost-effective, large-scale production

The unique properties of size, stability, and solubility for a single domain antibody allow breakthroughs in the field of cancer research, drug development, and therapy. With a variety of ways to use single domain antibodies and the ability to effectively target cancer cells, it’s no surprise that single domain antibodies are on the front lines in the fight against cancer.

References

  1. Samaranayake, H., Wirth, T., Schenkwein, D., Räty, J. K., & Ylä-Herttuala, S. (2009). Challenges in monoclonal antibody-based therapies. In Annals of Medicine (Vol. 41, Issue 5, pp. 322–331). Informa UK Limited. https://doi.org/10.1080/07853890802698842
  2. Vanlandschoot, P., Stortelers, C., Beirnaert, E., Ibañez, L. I., Schepens, B., Depla, E., & Saelens, X. (2011). Nanobodies®: New ammunition to battle viruses. In Antiviral Research (Vol. 92, Issue 3, pp. 389–407). Elsevier BV. https://doi.org/10.1016/j.antiviral.2011.09.002
  3. Scully, M., Cataland, S.R.,  Peyvandi, F., Coppo, P., Knöbl, P., Kremer Hovinga, J.A., Metjian, A., de la Rubia, J., Pavenski, K., Callewaert, F., Biswas, D., De Winter, H. and Zeldin, R.K. for the HERCULES Investigators. (2020). Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. https://pubmed.ncbi.nlm.nih.gov/30625070/