Monoclonal Antibody Therapy - Origins of Monoclonal Antibody Therapy

Origins of Monoclonal Antibody Therapy

Immunotherapy developed as a technique with the discovery of the structure of antibodies and the development of hybridoma technology, which provided the first reliable source of monoclonal antibodies. These advances allowed for the specific targeting of tumors both in vitro and in vivo. Initial research on malignant neoplasms found MAb therapy of limited and generally short-lived success with malignancies of the blood. Furthermore treatment had to be specifically tailored to each individual patient, thus proving to be impracticable for the routine clinical setting.

Throughout the progression of monoclonal drug development there have been four major antibody types developed: murine, chimeric, humanised and human.

Initial therapeutic antibodies were simple murine analogues, which contributed to the early lack of success. It has since been shown that these antibodies have: a short half-life in vivo (due to immune complex formation), limited penetration into tumour sites, and that they inadequately recruit host effector functions. To overcome these difficulties the technical issues initially experienced had to be surpassed. Chimeric and humanized antibodies have generally replaced murine antibodies in modern therapeutic antibody applications. Hybridoma technology has been replaced by recombinant DNA technology, transgenic mice and phage display. Understanding of proteomics has proven essential in identifying novel tumour targets.