Selected article for: "cell line and molecular weight"

Author: Liu, Justin K.H.
Title: The history of monoclonal antibody development – Progress, remaining challenges and future innovations
  • Document date: 2014_9_11
  • ID: 1e4dzy64_5
    Snippet: The first licenced monoclonal antibody was Orthoclone OKT3 (muromonab-CD3) which was approved in 1986 for use in preventing kidney transplant rejection [7] . It is a monoclonal mouse IgG2a antibody whose cognate antigen is CD3. It works by binding to and blocking the effects of CD3 expressed on T-lymphocytes. However, its use was limited to acute cases due to reported sideeffects (e.g. human anti-mouse antibody response) [8] . This is representat.....
    Document: The first licenced monoclonal antibody was Orthoclone OKT3 (muromonab-CD3) which was approved in 1986 for use in preventing kidney transplant rejection [7] . It is a monoclonal mouse IgG2a antibody whose cognate antigen is CD3. It works by binding to and blocking the effects of CD3 expressed on T-lymphocytes. However, its use was limited to acute cases due to reported sideeffects (e.g. human anti-mouse antibody response) [8] . This is representative of the relative lack of early clinical and commercial success of monoclonal antibodies. A major stumbling block was the fact that the production of early monoclonal antibodies was limited by whether or not there was a suitable myeloma cell line available (usually mouse or rat). Hybridomas may also be low yielding or genetically unstable [6] . More recently, many different expression systems for monoclonal antibodies have been tested, each with contrasting effects. For example, E. coli was found to be an excellent system for expression of antibody fragments such as single-chain variable fragments (scFv) and antigen-binding fragments (Fab) [9] . However, the synthesis of a relatively larger, full-sized antibody (i.e. consisting of 2 heavy chains and 2 light chains joined together by disulphide bridges giving a total molecular weight of~150 kDa) may be a step too far for such a relatively small microorganism, although the lack of glycosylating enzymes in E. coli may also prove to be beneficial for antibodies whose primary role is to block proteineprotein interactions as opposed to invoking downstream immune effector responses (e.g. the complement system), which can lead to potential immunogenic side-effects [10] . Also, the transformation efficiency, and thus the purity of produced humanised monoclonal antibodies, has been found to be low during the use of transgenic animals [11] . This concept involves the use of animal species for the production of humanised antibodies. For example, endogenous mouse IgG genes can be deleted from transgenic mice and replaced with human copies of the genes. After immunisation, mouse B-lymphocytes synthesise human versions of the respective antibodies and hybridomas can be produced. Its advantages include: cognate pairing of variable heavy and light domains (VH/VL pairing), an in vivo antibody maturation process which generates higher affinity binding regions and full-length IgG antibodies produced without the need for further cloning [12] .

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