Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5667_Библиотеки_им_академика_М_И_Перельмана

Although IgGs are the preferrable target as a therapeutic, IgMs are still widely stud­ied and show great promise as therapeutic drug candidates. One ascertainable dif­ference between the two is their relative size. IgMs are around 900 kDa on average, compared to IgG at 150 kDa[4]. IgMs form multivalent complexes that can allow for up to 10 or 12 binding sites compared to IgG with only 2. The outcome is that the affinity of IgMs is somewhat lower in comparison, but they are still able to neutral­ize foreign antigens by binding to multiple antigens at once, which is the concept of avidity[13, 14]. IgMs do not elicit engagement of effector mechanisms as IgGs do because IgMs do not bind to the Fc gamma receptor and do not exhibit ADCC activa­tion. However, IgMs have strong CDC activity and have a better binding affinity toward C1q than IgG[15]. IgMs binding to C1q have been shown by Sharp etal., and once IgM binds to its target antigen, it causes a conformational change in IgM. The conformational change allows for C1q to bind and trigger complement fixation[16]. Therefore, IgMs are also intensively studied as possible therapeutics alongside IgGs. IgM’s potential as a therapeutic drug has been shown in many patients’ case studies. Currently, there are roughly 20 IgM antibodies in clinical trials that target a variety of diseases, autoimmune disorders, and oncology[17]. The main issue that arises with the clinical use of IgMs is their lower efficacy rates in patient trials. This causes a problem with getting regulatory approval. After a closer look at the clinical trials of IgMs, it was concluded that the cause of lowered efficacy arose from the natural origins of the IgMs being tested; the IgMs tested had not gone through enough somatic mutations[17, 18]. Common antigens that are used consist of proteins, pro­teolipids, glycolipids, and glycoproteins. However, IgM antibodies are very advanta­geous when paired with glycans as an antigen due to IgM’s avidity and the fact that glycans are found to be exceptionally repetitive, especially on cancer cells. This allows for IgM antibodies to bind to multiple antigens on the outside of a tumor cell[19–21].