Therapeutic Protein Design and Antibody Characterization
Much research is being done to explore how antibodies can be used as therapeutic agents to treat diseases like cancer, autoimmune diseases, hematological diseases, and hematological diseases.
As research continues, new antibodies will be discovered and sequenced. Scientists can use our tool as a first step towards understanding how novel antibodies will engage with the immune system to combat diseases or pathogens. Knowing what Ig antibody isotype is essential information that is provided by our code. This feature can be verified in vivo via a T-Dependent Antibody Response (TDAR) assay.
For an antibody to be approved for therapeutic use, the mechanism of action must be well understood. Knowing which receptors the antibody binds to gives a good indication of what effector function(s) the antibody is likely to elicit, and this information can guide the researcher to what types of experiments to perform (examples include: performing a macrophage assay if ADCP is proposed as a mechanism of action, cytokine assay if ADCC is proposed as a mechanism of action, and biomarker testing if ADCC or CDC is proposed as a mechanism of action).
Similarly, this code can be used for protein engineering/design purposes. Similar to newly discovered antibodies, synthesized proteins require characterization and our code can be a tool for the initial learning steps.
Limitations to the current code would be the lack of specificity or distinction between IgG antibodies of the same subclass. Since our method organizes all the information based on IgG subtype, two different antibodies that happen to both be IgG1 would yield the same results for average FcyR affinities or effector functions. This may not be the case if assays have been conducted to improve FcyR binding affinities or efficacy of effector functions. In reality, all these parameters for antibodies within a single IgG subclass may not be identical and can vary.
In future iterations, we can add an input parameter where the user can state the fucosylation state.
The glycoform of the oligosaccharide attached to an IgG antibody plays an important role in its functionality, as the effector mechanisms mediated via FcγRI, FcγRII, FcγRIII, and C1q are severely compromised or abrogated in aglycosylated or deglycosylated forms of IgG13.
One example can be seen in the human IgG1 antibodies bearing the Fc-linked oligosaccharides; it has been shown that the antibodies lacking fucose show improved binding to FcγRIIIa and enhanced ADCC function compared to fucosylated ones13.