Murine antibody mouse derived

The majority of the proteins in clinical trials in August 1991 were monoclonal antibodies for treatment of sepsis or neoplasia (see Immunotherapeutic agents). Monoclonal antibodies are derived in most cases from mouse cell lines. This leads to the problem that the antibodies are recognized as foreign by the human immune system. Research efforts are directed toward humanizing antibodies so that these molecules can escape immune surveillance, for example, by the systematic replacement of murine-specific peptide sequences with human homologues while still maintaining the... 

For technical reasons, monoclonal antibodies initially were purely murine, i.e. derived from mouse cell lines. In clinical use, these murine antibodies met with limited success. Reasons for this include... 

Because most monoclonal antibodies that have been studied for tissue targeting are from mouse or, occasionally, from rat, the problem of antibody production to such foreign proteins always exists. While murine-derived mAbs are well tolerated for acute therapy, their use in chronic therapy is limited, due to severe human anti-mouse antibody response (HAMA) [231]. The HAMA response is elicited due to the foreign nature of the antibody itself. Molecular engineering is being utilized to replace the foreign components of the murine antibody with human antibody sequences to overcome their immunogenicity [232]. 

In 1975, Kohler and Milstein reported (1) that immortal cell lines secreting antibody of a single specificity could be produced by the artificial fusion of splenocytes derived from an immune mouse and tumour cells derived from a murine myeloma. They called these cell lines hybridomas and the product from them monoclonal antibodies. The development of monoclonal antibodies opened up huge possibilities in all areas of antibody use because reagents could be created with specificity to a single domain (epitope) on the target... 

Figure 9.7 Evaluation of biopharmaceutical X binding to mouse bone marrow derived cells, (a) Biopharmaceutical X binding to mouse bone marrow-derived cells was evaluated using flow cytometry. Mouse cells were incubated with biopharmaceutical X or the human ligand. Secondary antibodies that cross-reacted with both biopharmaceutical X and the natural human ligand were used to detect binding. Cells were stained with the secondary antibodies only, to detect non-specific binding (control), (b) Bone marrow derived mouse cells were stained as described above with a murine version of biopharmaceutical X and the murine ligand for the receptor. Secondary antibodies that cross-reacted with the murine version of biopharmaceutical X and the murine ligand were used to detect binding. See color insert.

The major drawback for plant-derived complex biopharmaceuticals is that the plant-specific xylosyl and fucosyl residues are attached to the core structure of N-gly-cans. Although Ghargelegue et al. [62] observed no immunogenic effects of a plant-derived murine monoclonal antibody in an animal study based on a mouse model, both residues are described in the Htera-ture as structures with high immunogenic potential [8, 9]. 

Monoclonal antibodies derived from murine hybridomas have been used in a variety of clinical applications, but some of the early promise could not be realized due to human anti-mouse immune reactions induced in treated patients. The concept of fusion of two biological systems for the synthesis of a specific monoclonal antibody has also been used for the creation of murine-human het-erohybridomas and for human-human hybridomas. In all these cases, because of the use of cells derived from blood sources, a very important characteristic has been inherited that significantly facilitates the scale-up of the cell substrate to very large cell number— the growth of single cells in free suspension. 

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