Antibody engineering for future therapeutics

摘要

Transgenics and protein display technology are underpinning a renaissance in the use of antibodies as therapeutic compounds, thirty years after the initial development of hybridomas. This paper reviews recent advances in these technologies and their impact on the clinical progression of antibody drugs. The discovery and development of hybridoma technology nearly thirty years ago heralded the possibility of a new age of monoclonal antibody therapeutics, with the promise of fulfilling Ehrlich's dream of the 'magic bullet', a drug that would search and destroy invading microbes or tumour cells. The development and commercialisation of such antibodies has not been straightforward however, and it is only in the last ten years that the number of FDA-approved monoclonal antibody therapeutics has begun to increase [Figure 1]. The initial approach in the 1970s was to try and develop murine monoclonal antibodies as drugs to treat human disease. This approach was largely unsuccessful as patients soon developed human antimouse antibodies (HAMA). This could result in neutralization of the therapeutic effect of the antibody or potentially anaphylaxis and allergy with re-treatment.