The antiglobulin response to therapeutic antibodies

The antiglobulin response to administered therapeutic monoclonal antibodies is currently one of the major limitations of antibody therapy. In the presence of a normally functioning immune system a response is inevitable after 1-2 weeks of treatment with most agents. The anti-idiotype arm of the response will inhibit the binding of antibody to target antigen, whilst both this and the anti-isotype component act to accelerate antibody clearance. Although the antiglobulin response appears to follow the rules governing immunity to soluble protein antigens the idiotypic epitopes of cell-binding antibodies seem to be particularly immunogenic. The consequence of this has been the failure to induce tolerance to therapeutic antibodies by conventional approaches and, in turn this has provided much of the stimulus to the technology of antibody 'humanisation'. It is still uncertain, however, if even a humanised antibody will remain invisible to the immune system.