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Production of Human and Humanized Antibodies - Human antibodies are currently produced by the following methods:

(i) fusion of mouse myeloma cells with human lymphocytes (blast cells in peripheral blood lymphocytes)

(ii) immortalization of human cells by Epstein Barr virus. Both the methods have limitations. Human mouse hybrid cells have a tendency for preferential loss of human chromosomes, making them unstable. Similarly, Epstein-Barr virus does not allow preferential immortalization of blasts engaged in antibody response.

In view of these difficulties, humanizing of rodent monoclonal antibodies through genetic engineering is the most practical approach, which is being evolved and used for the production of mouse human chimeric monoclonal antibodies to be used for tumour therapy or for manipulation of human immune system or against cell surface antigens. The humanized chimeric antibodies combine the rodent variable regions with the human constant (or constant + variable) framework regions

To further reduce the immunogenicity of rodent elements, humanized antibodies have been produced, which retain only the antigen binding complementarity determining regions (CDRs) from the rodent in association with human framework regions. In another approach transgenic mice carrying human genes for V, D, J and C regions have been produced. These can be used for the production of human antibodies directly by hyperimmunization.