Complement as effector system in cancer immunotherapy

The contribution of the complement system to the control of tumour growth has been neglected for a long time as the major emphasis has been put mainly on cell-mediated immune response against cancer. With the introduction of monoclonal antibodies in cancer immunotherapy complement has come into play with a great potential as effector system. Complement has a number of advantages over other effector systems in that it is made of molecules that can easily penetrate the tumour tissue and a large majority, if not all, of the components of this system can be supplied locally by many cells at tissue site. Further advances are being made to increase the anti-tumour efficiency of the complements system using C-fixing antibodies that are modified in the Fc portion to be more active in complement activation. Another strategy currently investigated is essentially based on the use of a combination of two antibodies directed against different molecules or different epitopes of the same molecule expressed on the cell surface in order to increase the number of the binding sites for the antibodies on the tumor cells and the chance for them to activate complement more efficiently. One of the problems to solve in exploiting complement as an effector system in cancer immunotherapy is to neutralize the inhibitory effect of complement regulatory proteins which are often over-expressed on tumour cells and represent a mechanism of evasion of these cells from complement attack. This situation can be overcome using neutralizing antibodies to target onto tumour cells together with the specific antibodies directed against tumor specific antigens. This is an area of active investigation and the initial data that start to be available from animal models seem to be promising. (c) 2007 Published by Elsevier B.V.