Mimicking nature’s antibodies

Monoclonal antibodies

Monoclonal antibodies (mAbs) synthesised in the laboratory aim to mimic natural antibodies which are produced by the body to selectively and specifically target pathogenic proteins or antigens in response to infection and neutralise them. When used as a therapeutic, mAbs employ the same approach to seek out and neutralise the target of interest.

Over the past three decades, mAbs have revolutionised the treatment of infectious diseases, cancer and chronic immunological diseases. Building on our long-standing heritage in this field from Cambridge Antibody Technology (CAT) and MedImmune, we harness our extensive antibody discovery and protein engineering platform to design mAbs for therapeutic applications. For example, we are able to optimise mAbs using our proprietary extended half-life technology which can extend the length of protection of the mAbs in the body. We are also using these platforms to design mAb fragments and bispecific mAbs, which can potentially offer wider therapeutic benefits unique to these modalities.

In addition to uncovering innovative ways to incorporate antibodies in cutting-edge therapies and diagnostics across oncology, we are developing novel mAbs that can target different drivers of inflammation in a number of respiratory and immunological conditions such as asthma and chronic obstructive pulmonary disease (COPD), as well as against infectious diseases such as respiratory syncytial virus (RSV) and COVID-19.^1,2

Fragment antibodies

Fragment antibodies, as the name suggests, are fragments of the binding end of a monoclonal antibody (mAb) and can be a small but mighty tool to fight disease. While mAbs range from around 150kDa in size, fragment antibodies as small as 3kDa have been used in various applications.

Their small size helps access difficult-to-reach therapeutic targets on tissues and cells as well as penetrate tumours more effectively.^3,4 These small fragments can also be useful for rapidly blocking signalling molecules or receptors. Because they do not have the bulk of a whole antibody, fragments can also minimise other downstream effects on the immune system.³

Fragment antibodies are emerging as great tools in imaging and diagnostics because they are capable of detecting cellular proteins with high affinity and specificity. They can be easily linked to radioisotopes, fluorescent molecules or enzymes that tag specific biomarkers in patients. They also have a shorter half-life in the body which results in faster clearance and may result in fewer risks of side effects from potentially invasive diagnostic agents.

Fragment antibodies can also be produced in simpler steps compared with more complex antibodies, making them potentially faster to produce in high yields.

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References

1. Griffin MP, Yuan Y, Takas T, et al. Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants [published correction appears in N Engl J Med. 2020 Jul 29;:]. N Engl J Med. 2020;383(5):415-425. doi:10.1056/NEJMoa1913556.

2. Zost SJ, Gilchuk P, Case JB, et al. Potently neutralizing and protective human antibodies against SARS-CoV-2 [published online ahead of print, 2020 Jul 15]. Nature. 2020;10.1038/s41586-020-2548-6. doi:10.1038/s41586-020-2548-6.

3. Bates, Adam, and Christine A. Power. 2019. “David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments.” Antibodies (Basel, Switzerland) 8 (2). https://doi.org/10.3390/antib8020028.

4. Kholodenko, Roman V., Daniel V. Kalinovsky, Igor I. Doronin, Eugene D. Ponomarev, and Irina V. Kholodenko. 2019. “Antibody Fragments as Potential Biopharmaceuticals for Cancer Therapy: Success and Limitations.” Current Medicinal Chemistry 26 (3): 396–426.

Veeva ID: Z4-66599
Date of preparation: August 2024