[Immunoconjugates, drug-armed antibodies to fight against cancer]

Abstract

Monoclonal antibodies constitute a growing class of therapeutic agents. They are classically used in combination with chemotherapeutic drugs for cancer treatment. The concept of coupling a cytotoxic agent to an antibody can be viewed as a means to confer a selectivity for tumoral cells to highly cytotoxic drugs which cannot be used in human, or a higher power to antibodies which have a low anti-tumoral activity on their own. Gemtuzumab ozogamicin is the only drug-armed antibody available on the market, for the treatment of acute myeloid leukaemia. Other immunoconjugates are currently under clinical development. The most used cytotoxic agents derive from calicheamicin, maytansin and auristatin, compounds which are 100 to 1 000 fold more toxic than the classical chemotherapeutic drugs. Today, we know that the efficacy of an immunoconjugate depends not only on the coupled cytotoxic agent, but also on the selected target, the coupling method and the linker.