[Future perspectives on tumor-specific immunotherapy using hapten-reactive T cell activity].

Recent studies concerning cellular and molecular mechanisms of T cell-mediated immunity have revealed the involvement of various types of lymphokines. Irrespective of which types of lymphokines and cell-cell interactions among various T cell subsets are involved in the implementation of host immune responses against tumor, the feasible and practical approach is to use both molecular and cellular mechanisms for the augmented induction of effector T cell activity against tumor-resistant antigens (TRA). We have demonstrated previously that the in vivo effector T cells comprise 2 subsets of TRA-specific non-cytolytic CD4- and CD8-positive helper T cells, both of which release lymphokines and activate macrophages as an ultimate anti-tumor cytocidal effector. We have also defined conditions under which enhanced anti-tumor immunity can be obtained by pre-inducing potent helper T cell activity reactive to a certain antigenic determinant such as trinitrophenyl (TNP) residue of muramyl dipeptide (MDP)-derivatives as hapten, and immunized with tumor cells coupled with the corresponding haptenic determinant. This system induced most efficient and physiological cellular and molecular mechanisms responsible for the generation of tumor-specific effector T cell activity in vivo by virtue of the close linkage of hapten-reactive helper T cells and TRA-specific effector-precursor T cells in the microenvironment of hapten-coupled tumor cells. We have subsequently demonstrated that this protocol resulted in enhanced in vivo tumor protective immunity but also was applicable to the immunotherapy whereby a growing solid tumor as well as disseminated leukemia cells could be effectively eradicated in mice. Thus, these results emphasize the role of hapten-reactive helper T cell in augmenting tumor-specific immunity, and this protocol provides an effective maneuver for tumor-specific immunotherapy in human in future.