Tumor-specific immunotherapy by active immunization with haptenic muramyl dipeptide derivative-coupled tumor cells.

The theoretical basis and practical manipulation of cellular collaboration mechanism responsible for enhanced induction of tumor-specific immunotherapeutic potential were reviewed. Enhanced generation of tumor-specific in vivo protective immunity could be obtained by immunizing tumor cells coupling highly immunogenic additional antigens to hosts in which helper T cell activity against these antigens is already induced. MDP haptens newly synthesized exhibited cross-reactivity with BCG and functioned as appropriate tumor cell-modifying reagents in BCG-sensitized individuals. With the use of these new MDP haptens, the above approach for enhanced tumor immunity was successfully applied to tumor-specific immunotherapy models. When tumor-bearing hosts had been sensitized to BCG, the growth of tumor cells in a solid tumor mass or in metastasized or disseminated form were effectively inhibited by active immunization with MDP hapten-modified tumor cells. Thus, these results reinforce the theoretical framework of the approach for enhanced induction of tumor immunity. The protocols which were developed in these studies also provide an effective maneuver for tumor-specific immunotherapy.