29.03.2021 duration: 4 min

Afucosylated antibodies and the difference to recombinant antibodies

Afocusylated antibodies are recombinant monoclonal antibodies with increased antibody-dependent cellular cytotoxicity. That is why we also use the designation ADCC antibody. These are Y-shaped proteins produced by the human body. As they are able to identify and neutralize foreign objects – in other words viruses – they play a major contributing role in keeping our body and immune system healthy. 

Their ability to target almost any cell surface or secreted molecule with remarkable efficacy and safety contributes to their popularity and there is a tremendous amount of research being conducted around antibodies.

Today, various types of antibodies can be reproduced and cultivated in labs to then be utilized in a number of medical and pharmaceutical applications. In fact they represent the fastest growing group of biotherapeutics both in terms of clinical trials and in global sales revenue.

Afucosylated & recombinant antibodies – a comparison

Since afucosylated & recombinant antibodies have been approved and commercially used for the first time in the late 1980s, artificially cultivated antibodies have seen a steady rise in terms of utilization. Currently, there are several hundred products in development, many of which are targeting multiple indications. This whole process is called “Glycoengineering of Antibodies for Modulating Functions”.

So what’s the impact of glycosylation on monoclonal antibodies (mAbs)? Do recombinant and afucosylated antibodies live up to the hype surrounding them and what are (potential) fields of application?

Let’s start with recombinant antibodies (rAbs): Those are monoclonal antibodies that are generated in vitro using synthetic genes. In the past decade alone, several antibodies have been developed for a number of therapeutic applications and several known formats of recombinant antibodies are produced, with each of the formats having a slightly different potential in applications and fields of research. The most commonly used recombinant antibodies are scFv, Fab fragments and bispecific antibodies. An advantage of recombinant antibodies (rAbs) is their high affinity compared to low-affinity bodies as they bind strongly to the antigen and maintain better under difficult conditions.

Afucosylated antibodies on the other hand are engineered monoclonal antibodies (mAbs) with the oligosaccharides in the antibody’s Fc region missing fucose sugar units, a fact that contributes to the increase of the antibody-dependent cellular cytotoxicity (ADCC).

Enhaced ADCC activity is important to push the efficacy of cancer antibodies, however, as a result of nonspecific IgG competing with the drugs for binding to FcγIIIa on natural killer cells (NK cells) a number of already approved cancer antibodies have less ADCC than could be desired. And this is where the afucosylated monoclonal antibody comes in: It overcomes this problem through improved FcγIIIa binding – the results are (antibody-dependent cellular cytotoxity) ADCC enhanced antibodies. 

Usage of afucosylated antibodies and recombinant antibodies

Recombinant antibodies are not only easily and reliably reproduced but offering a number of additional advantages, which is why they are increasingly popular in both medical and research applications. They are primarily utilized for targeting:

  • maligne tumor cells
  • cancer cells
  • autoimmune disorders, and a 
  • host of other diseases. 

More currently speaking, they are being cultivated on the basis of genetically modified eColi and CHO (Chinese Hamster Ovary) cells to be applied in mRNA corona vaccines.

Afucosylated antibodies for therapeutic use show more potency in vitro and in vivo than their fucosylated counterparts – such as recombinant antibodies –  resulting in the likelihood of making them more powerful and efficient in designing next-generation therapeutic antibodies. Thanks to their low fucose content, afucosylated antibodies exhibit an increased killing activity against tumorigenic and infected cells.

Interested in recombinant antibodies?

    Production of afucosylated recombinant antibodies

    At evitria, recombinant antibodies are expressed based on the clients’ individual needs and requirements. They are generated in vitro using synthetic genes derived from CHO (Chinese Hamster Ovary) cells.

    Over the years those have remained a popular choice with many biopharmaceutical manufacturers as they are ideal for large-scale cultures while at the same time offering high recombinant protein yields and specific productivity: CHO cells can produce recombinant protein on a scale of 3-10 grams per liter of CHO cells culture

    ADCC antibody

    Afucosylated antibodies or ADCC antibodies are merely modified recombinant antibodies with the benefit of exhibiting an artificially decreased fucose content, which leads to the effector function of ADCC and results in an elevated killing activity against tumorigenic and infected cells. At evitria, antibody expression takes place using the same CHO cells and DNA as native antibodies.

    afucosylated monoclonal antibody expression by evitria

    The benefits of the GlymaxX® technology

    Thanks to their efficient and reliable ability to target almost any cell surface or secreted molecule, genetically modified as well as native antibodies offer unparalleled opportunities for the biopharmaceutial and life-science industries. This furore is causing a high demand that can be easily met, thanks to easy cultivability and ever improving cultivation systems and processes.

    Speaking of which: The state-of-the art GlymaxX® platform enables evitria to transiently express both native and afucosylated variants using the same CHO cell line, the same DNA, and without any amino acid sequence modifications. So while alternative afucosylation approaches rely on Fc mutations with the risk of immunogenicity, evitria’s use of GlymaxX® produces the same yields and stability as native antibodies – but ruling out the danger of potential immune response.

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