Surface immunoglobulin of B-lymphocytic tumours as a therapeutic target

The surface immunoglobulin of B-lymphocytic tumours is well characterized at the molecular level and in its idiotypic determinants offers antigenic targets which are effectively tumour-specific. Anti-idiotype antibodies raised individually for each tumour have been used for passive serotherapy in animals and man. The advent of monoclonal technology has added further precision, and can readily provide the large quantities of antibody which might sometimes be necessary. However, the therapeutic use of unmodified anti-idiotype has yielded a significant remission in only a minority of cases. Some factors thwarting the antibody can be readily identified; prominent among these are extracellular idiotypic immunoglobulin and antigenic modulation. Another major factor is our ignorance of appropriate effector mechanisms to be recruited, with one candidate mechanism being the activation of immunological suppressor circuits. Without such knowledge there is a large arbitrary element in the selection of antibody isotype, doses and schedules. Some groups suspect that antibody derivatives will eventually prove more effective than the native molecules. Univalent, chimeric univalent and toxin-bearing antibodies are among those being investigated. Monoclonal and molecular genetic technologies may play an increasing role in the engineering of such derivatives. The fast-growing animal lymphomas presently available as models cannot mimic more than a tiny fraction of human lymphomas. So the arena in which antibody therapy of B lymphoma will be decided is the clinic. Here the relatively innocuous nature of antibody treatment is a tremendous boon. However, with the mechanisms involved being multiple, complex and only partially understood we are unlikely to be favoured with rapid answers.