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Therapeutic IgM Antibody in Clinical Trials

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IgMs are pentameric or hexametric macro-immunoglobulins and have been highly conserved during evolution, which are the first antibodies secreted following exposure to foreign antigens. The high binding activity of IgM antibodies renders them particularly efficient at binding non-protein antigens such as carbohydrates or lipids as well as antigens present at low levels. Therefore, several naturally occurring IgM antibodies have been explored as therapeutics in clinical trials, while engineered IgM antibodies with enhanced binding and additional functional properties are being evaluated in humans. Therefore, therapeutic IgM attracts more attention from Creative Biolabs, an advanced biotech company focused on the field of therapeutic molecule development. Based on our established and mature platforms, we have gained remarkable achievements in the research of IgM. We are glad to share our experience with our clients over the world.

Introduction of IgM

IgM is initially produced as a surface-bound molecule and is expressed in early B cell differentiation. Later in the immune response, IgM is produced by plasma cells and secreted as soluble pentamers or hexamers with a molecular weight of over 1000 kDa. Due to the polyvalent nature of IgMs, they may exhibit higher avidity for antigen than IgG or IgA, a kind of bivalent antibody. Besides neutralizing pathogens, IgM antibodies are highly effective at engaging complement to target lysis of cells and pathogens.

Natural IgM in immune equilibrium. Fig.1 Natural IgM in immune equilibrium. (Kaveri, 2012)

Function of IgM

IgMs have important and diverse roles in health and disease, while the most important function of IgM as the first line of defense for protection against invading microbes has been extensively accepted. The potent ability of IgM antibodies to fix complement and opsonize particles makes them particularly effective against bacteria and viruses. Moreover, Their hexameric or pentameric structure allows the highly avid binding of complement components to IgM, and therefore IgMs are able to fix complement substantially better than IgGs, which provide huge application potential in clinical therapeutics.

Therapeutic Uses of IgM

Many research suggests that IgM antibodies also have the potential to provide therapeutic benefits like IgG and especially target infectious disease and autoimmune disease antigens. Moreover, most IgMs target antigens are poorly immunogenic and for which it has been difficult to generate IgG mAbs such as lipopolysaccharides (LPS), gangliosides, proteolipids, and glycans. Therefore, IgM is regarded as an effective adjunctive supplement of therapeutic IgG and IgA. However, compared with over 100 IgG-based products approved by FDA, only about 20 IgM antibodies have been tested in humans, which results in difficulties in expression and purification due to large molecular weight.

History of selected IgM human clinical trials. Fig.2 History of selected IgM human clinical trials. (Keyt, 2020)

With a focus on IgM antibodies and IgM platforms, more and more therapeutic IgMs have been promoted into clinical trials. We believe that IgMs can provide new opportunities for more effective therapeutics. If you are interested in the research of therapeutic IgM clinical trials, or want more details in the research of the therapeutic molecular field, please feel free to contact us.

References

  1. Kaveri, S. V.; et al. Natural IgM in immune equilibrium and harnessing their therapeutic potential. The Journal of Immunology. 2012, 188(3), 939-945.
  2. Keyt, B. A.; et al. Structure, function, and therapeutic use of IgM antibodies. Antibodies. 2020, 9(4), 53.

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