Tumor immunotherapy with bispecific antibodies

Bispecific monoclonal antibodies (Bi-MAb) which recognize a tumor-associated antigen (TAA) with one arm and bind to a trigger molecule on an immunologic effector cell with the second arm, open the potential for specific activation of cytotoxic effector cells of the immune system (NK cells, T lymphocytes, macrophages) at the tumor site. SCID mice bearing hetero-transplanted Hodgkin's tumors were cured even at the stage of disseminated disease by treatment with the appropriate Bi-MAbs and human lymphocytes, establishing this approach as one of the most effective models of immunotherapy for human tumors. Several clinical trials employing different target and effector cells for the evaluation of the feasibility, toxicity, and efficacy of Bi-MAb therapy have recently been started. The low toxicity and surprising efficacy of the systemic application of an NK-cell-activating Bi-MAb in patients with refractory Hodgkin's disease encourage further clinical trials of this novel immunotherapy in patients with malignant tumors refractory to standard treatment.