Humanization technologies, antibody molecules

The first two antibodies our group tried to express in this vector system within mammalian cells had mistakes in the genetic material that coded for variable regions and, consequently, did not express any antibody at all. The first antibody that was produced by recombinant technology at IDEC using this vector system was in early 1991. It was supposed to be a chimeric anti-CD4 antibody, but the antibody secreted by the cells did not bind to CD4. CD4 is a surface molecule on the leukocytes known as T cells. A primatized antibody (a chimeric antibody where the variable domains are isolated from a cynomol-gus monkey see Figure 32.2) to CD4 was produced later that year. That antibody ended up in clinical trials in humans at the same time as Rituxan. 

The advent of recombinant DNA technology led to the development of antibodies and fragments that are tailored for optimal behaviour in vivo [7,8]. Humanized and chimeric antibodies can be constructed to circumvent the human anti-mouse antibody response elicited by mouse antibody treatment of patients, which severely hampers the application of these powerful molecules. The treatment of rheumatoid arthritis patients with doses of as high as 10 mg kg cA2 chimeric antibody specific for TNFa [9], emphasizes that at present the production and purification methods for these proteins have been optimized to such extent that clinical studies can be considerably intensified. 

Since it is impossible to obtain human mAbs from technologies such as those outlined above, other alternatives have been sought to enable the production of molecules with the appropriate variable domains of heavy and light chains, as well as its correct alignment, to guarantee the same affinity and specificity of the murine antibody, but with the human... 

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