Antibody therapeutics have emerged as a leading frontier in modern medicine, targeting a range of diseases from cancer to autoimmune disorders to infectious diseases. The first monoclonal antibody (mAb), muromonab-CD3, was approved by the US Food and Drug Administration in 1986 to prevent kidney transplant rejection. This is a mouse IgG2a mAb that binds to and inhibits the activity of CD3 expressed on T-lymphocytes.1
Since then, antibody engineering has undergone significant advancements in reducing side effects and increasing specificity. Early antibodies, like muromonab-CD3, often caused unwanted immune responses due to their murine origins. Modern engineering techniques, however, have led to the development of fully human or humanized antibodies, significantly improving their safety profiles by reducing immunogenicity.
By 2025, the mAb drug market is predicted to generate a revenue of $300 billion, which does not account for newer formats such as antibody-drug conjugates, bispecific antibodies, antibody fragments, radiolabeled antibodies, antibody-conjugate immunotoxins, immunoconjugates and Fc-Fusion proteins.2,3
Expanding Formats: Beyond Monoclonal Antibodies
While monoclonal antibodies are still the cornerstone of antibody therapeutics, newer formats have emerged that broaden their potential applications. Bispecific antibodies, for instance, are engineered to bind two different antigens, potentially improving therapeutic outcomes by simultaneously engaging multiple targets. This technology is particularly promising in cancer immunotherapy, where bispecific antibodies can link T-cells to cancer cells, promoting targeted immune responses.
Additionally, antibody fragments, such as single-chain variable fragments (scFvs) and Fab fragments, offer advantages in terms of tissue penetration and reduced production costs. These smaller antibody formats are especially useful in diagnostic applications or therapeutic scenarios where full-length antibodies may be too large to effectively reach their targets.
The introduction of antibody-drug conjugates (ADCs) has further expanded the possibilities of antibody therapeutics. ADCs link a cytotoxic drug to an antibody, allowing for targeted delivery of the drug to cancer cells. This precise targeting minimizes damage to healthy tissues, offering a more controlled approach to chemotherapy. Examples like trastuzumab emtansine (Kadcyla) have demonstrated the success of this approach in treating HER2-positive breast cancer.
The development of radiolabeled antibodies and immunoconjugates has also shown promise, particularly in oncology. Radiolabeled antibodies can deliver radiation directly to tumors, improving the precision of radiotherapy. Immunoconjugates, which couple antibodies with toxins or enzymes, have potential in targeting specific cell populations, further enhancing the precision of antibody-based therapies.
Examples
Cancer: mAbs are used to target specific tumor antigens, helping to treat cancers like breast cancer (e.g., trastuzumab/Herceptin) and lymphoma (e.g., rituximab).
Autoimmune diseases: Therapies like adalimumab (Humira) are used to treat conditions like rheumatoid arthritis by targeting TNF-α, a pro-inflammatory cytokine.
Infectious diseases: Antibodies like palivizumab are used to prevent respiratory syncytial virus (RSV) infections in high-risk infants.
References:
Liu, K. H. (2014). The history of monoclonal antibody development – Progress, remaining challenges and future innovations. Annals of Medicine and Surgery, 3(4), 113-116. https://doi.org/10.1016/j.amsu.2014.09.001
Lyu, X., Zhao, Q., Hui, J., Wang, T., Lin, M., Wang, K., Zhang, J., Shentu, J., Dalby, P. A., Zhang, H., & Liu, B. (2022). The global landscape of approved antibody therapies. Antibody Therapeutics, 5(4), 233-257. https://doi.org/10.1093/abt/tbac021
Lu, RM., Hwang, YC., Liu, IJ. et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 27, 1 (2020). https://doi.org/10.1186/s12929-019-0592-z
