Afucosylated monoclonal antibodies

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Afucosylated monoclonal antibodies are monoclonal antibodies engineered so that the

oligosaccharides in the Fc region of the antibody do not have any fucose sugar units. When antibodies are afucosylated, antibody-dependent cellular cytotoxicity
(ADCC) is increased.

Background

Most approved monoclonal antibodies are of the

natural killer cells. Afucosylated monoclonal antibodies overcome this problem through improved FcγIIIa binding.[1]

Approaches

The Swiss company GlycArt Biotechnology developed a system using

GnTIII. The effect of this overexpression is to block the formation of fucosylated oligosaccharides on the expressed antibodies. This technology was first reported in 1999 and was the basis of GlycArt Biotechnology.[2]

Roche acquired GlycArt in 2005 in order to acquire technology to afucosylate antibodies. GlycArt Biotechnology had been founded in 2000 as a spin-out company of the Swiss Federal Institute of Technology in Zurich. The first commercial product from the GlycArt acquisition was obinutuzumab, which as Gazyva gained FDA approval in November 2013 for the treatment of chronic lymphocytic leukemia.[3][4][5]

Kyowa Hakko Kirin's "Potelligent" platform uses a CHO cell line in which

Fc region. The company gained marketing approval in Japan in April 2012 for a monoclonal antibody drug called mogamulizumab which was developed using the platform.[6] The Company's technology was first reported in 2004.[7]

Applications of afucosylated antibodies

Afucosylated antibodies are intensely used in the field of advanced medicine, also due to their high ADCC (antibody-dependent cellular cytotoxicity). This makes them effective in binding to specific targets while minimizing damage to surrounding tissue.

Some of the fields in which afucosylated antibodies are used or considered for application are:

  • cancer immunotherapy
  • autoimmune diseases
  • Infectious diseases

Furthermore, afucosylated antibodies are used as diagnostic tools and play a role in the development of personalized medications.[8]

References

  1. S2CID 24803037
    .
  2. S2CID 20078393
    .
  3. ^ "Roche - Roche acquires Swiss based GlycArt Biotechnology to strengthen expertise in therapeutic antibody research". roche.com. Archived from the original on 2015-02-05. Retrieved 2015-04-29.
  4. ^ Presentation: GlycArt Biotechnology AG From Inception to trade sale – and what happened after... by Dr. Joël Jean-Mairet. Brussels, March 31, 2011
  5. S2CID 40983655
    .
  6. S2CID 3722081
    .
  7. S2CID 40137283
    .
  8. ^ Schofield, Desmond (November 23, 2023). "Afucosylated recombinant antibodies". evitria.com. Retrieved November 11, 2023.
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