Therapeutic human antibody treatments are one of the largest growing pharmaceuticals today. These antibodies are sometimes also referred to as mAbs, or monoclonal antibodies. Monoclonal antibody therapy is a form of immunotherapy which uses monoclonal antibodies to bind to particular cells or proteins, with the objective of stimulating a patient’s immune system to attack targeted cells. The mAbs used help develop drug therapies for a broad range of diseases, including varies cancers, such as bladder cancer, metabolic diseases, and auto-immune diseases. Crohn’s disease, Asthma, and Rheumatoid arthritis are just a sample of auto-immune diseases that monoclonal antibody therapy can help treat or improve (5). Immunoglobulin G(IgG) is one of the most popularly used mAbs, and as of 2021 out of the total antibody drugs approved in the United States of America and European Union, ~60% of them contained hIgG1, and ~17% contained hIgG4(3).
Immunoglobulin G1 and Immunoglobulin G4 account for approximately 73% of the total IgG in an adult human body (1). IgG1 making up about 70%, with IgG4 making up around 3%. IgG1 tends to be the most popular choice for developing human antibody therapeutics due to its relatively high thermostability, monomeric nature, and a structurally flexible hinge region, only containing two disulfide bonds. (1) Typically, IgG4 antibodies have a reduced effector function relative to the IgG1 form, which has been shown to prevent the hexamer formation of human IgG1 and IgG3, ultimately preventing C1q1 from binding by steric interference (4). This feature could be deemed useful in a small section of mAbs drug therapies with a goal of preventing particular cells or proteins from experiencing apoptosis. Human IgG1 also contains the unique ability to bind all types of human FcyR (2).
One example of how Intravenous immunoglobulin (IVIg) can be used in autoimmune patient treatment would be best shown in use with Crohn’s disease patients. Crohn’s disease is often seen as an overactive inflammatory immune response. When patients are given IVIg, which contain normal IgG, which are then developed to target and decrease the bodies overactive inflammatory response.
Both researchers and doctors alike have a need for measuring the amount of human IgG1 or IgG4 present in a subject. This would be to test the stability, once given to a subject, in order to measure the amount, present after desired times. This would help us to determine the pharmacodynamics and pharmacokinetics of a particular drug or serum containing human IgG1 and IgG4.
Due to the fact that primate and human antibodies are highly homologous, it can become difficult to distinguish the human antibody drug from the endogenous primate antibodies present in a serum or plasma by the way of a traditional human IgG-specific immunoassay. However, now with Oxford’s new Recombinant (therapeutic) Human IgG ELISA kit, human IgG1 or IgG4 can be accurately quantified in serum or plasma samples. This kit has the ability to be used for both human samples, as well as other preclinical test species such as mice, rats, rabbits, guinea pigs, etc.…
Sources:
- Thomson, Christy A. “IgG Structure and Function.” ScienceDirect, Encyclopedia of Immunobiology, 1. https://www.sciencedirect.com/science/article/pii/B9780123742797050025.
- “9- Therapeutic Antibody Classes.” Science Direct, Therapeutic Antibody Engineering , 27 Mar. 2014, https://www.sciencedirect.com/science/article/pii/B9781907568374500099.
- Lai, Pin-Kuang, et al. “Differences in Human IgG1 and IgG4 S228P Monoclonal Antibodies Viscosity and Self-Interactions: Experimental Assessment and Computational Predictions of Domain Interactions .” National Library of Medicine, MAbs, 8 Nov. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583000/.
- Lilienthal, Gina Maria, et al. “Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcy Receptor Activation Pathways .” Frontiers in Immunology, 9 May 2018, https://www.frontiersin.org/articles/10.3389/fimmu.2018.00958/full.
- “The Role of Antibody Therapies for Treating and Preventing Diseases.” AstraZeneca, 27 Oct. 2021, https://www.astrazeneca.com/what-science-can-do/topics/covid-19/role-of-antibodies.html.