Problems and prospects in the use of lymphoma idiotypes as therapeutic targets

The infusion of anti‐idiotypic antibody in patients with lymphoma has proved a relatively innocuous procedure, but in general has yielded only partial, short‐lived remissions of disease. A major problem is that xenogeneic antibody is simply not well‐fitted to destroying mammalian cells: complement and celluar effectors (K cells and phagocytes) are not efficiently recruited, and the target cells in any case present some excellent defense mechanisms. Antigenic modulation is particulary prominent among these defenses and we present evidence here for modulation of idiotype being much more efficient in vivo than in vitro. Two broad types of antibody derivative are under development to improve the killing of neoplastic targets. One type relies on recruiting natural effectors, and is exemplified by univalent chimeric antibody. The other relies on delivering an exogenous effector such as a drug or toxin, and is exemplified by bispecific anti‐Id/anti‐saporin F(ab'γ) 2 antibody. Both types of derivative have been able to suppress animal lymphoma to the extent that tumor escape occurs largely through the emergence of idiotype‐negative mutants.