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AAT Bioquest

How are monoclonal antibodies classified?

Posted October 10, 2023


Answer

Monoclonal antibodies can be produced using different methods and are classified into four types based on their origin: murine, humanized, chimeric, and fully human antibodies. 

  1. Murine monoclonal antibodies are fully derived from mice (both the light and heavy chains are of mouse origin). These were the first antibodies to be produced at lab-scale due to the discovery of hybridoma technology. However, only a small amount of these antibodies are still utilized in therapy in modern times due to their low compatibility with the human immune system. 
  2. Chimeric monoclonal antibodies are composed of human constant regions and mouse variable regions. More specifically, these antibodies consist of more than 65% human antibodies, which are fused with mouse antibodies. The constant regions determine the antibody’s effector functions, and the variable regions display antigen specificity. As an example, infliximab is a chimeric antibody which targets TNF-a and is used to treat inflammatory disorders such as rheumatoid arthritis. 
  3. Humanized antibodies primarily are of human sequence (consist of more than 90% human antibodies), and are combined with only a small region of mouse sequence in the CDRs. Humanizing antibodies reduces the immunogenetic correlated with murine antibodies. These antibodies are produced by grafting portions of mouse antibodies onto human antibodies. As an example, trastuzumab is a humanized antibody which is used to treat HER2-positive breast cancer. 
  4. Fully human monoclonal antibodies are completely derived (100%) from human sequences (in both the variable and constant regions). These antibodies were produced to maximize compatibility with the human immune system, as well as reduce immunogenicity. They are generated by inserting the genetic material of mouse antibodies into human antibodies. Adalimumab is a fully human antibody which targets TNF-a and is utilized to treat autoimmune diseases such as psoriasis.       
Additional resources

The immunogenicity of humanized and fully human antibodies

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