Anti-idiotypic therapy of leukemias and lymphomas

Idiotypic determinants of the Ig expressed by the majority of B cell tumors present an attractive target for immunotherapeutic manipulations. The idiotypic Ig is molecularly defined and the behavior of the target cells placed under anti-idiotypic attack might have broader implications for cancer immunotherapy. Simple administration of monoclonal antibody reactive with these determinants clearly has only a limited effect on tumor load, due largely to the multiplicity of strategies by which the tumor cell can avoid such attack. These include modulation, change in idiotypic determinants due to somatic mutation, and complete loss of expression at the cell surface. If the first antibody treatment can be made more effective, for example by tailoring molecules to recruit available effector mechanisms more efficiently, or by the use of antibodies capable of delivering a lethal hit via a toxin, the tumor cell will presumably have less opportunity to escape. A second strategy is to immunize the tumor-bearing host with idiotypic Ig obtained from tumor cells. Once in place, such an immune response should suppress tumor growth on a continuing basis. In animal lymphoma, this approach appears to prolong survival although some of the escape mechanisms encountered for passive antibody therapy are apparently operative for active therapy. Study of these mechanisms should allow insight into how cells control expression of idiotypic determinants at the cell surface and open the possibility of further therapeutic intervention. A combined approach to the treatment of human lymphoma might be envisaged whereby tumor load is reduced by passive antibody, thus leaving the immune system relatively unscathed, and even perhaps releasing natural antitumor responses which could be further stimulated by immunization.