Treatment of Hodgkin's disease with bispecific antibodies.

Bispecific monoclonal antibodies (Bi-MAbs) with dual specificity for tumor-associated antigens (TAA) and a triggering molecule of an immunologic effector cell, respectively, open the possibility to specifically target to and activate cytotoxic effector cells (macrophages, T-cells, NK cells) at the tumor site. Using appropriately designed Bi-MAbs and unstimulated human NK cells and T-cells, respectively, we were able to cure SCID mice xenografted with human Hodgkin's tumors. This approach was also effective in disseminated tumors and when treatment was delayed until three weeks after the inoculation of the tumor, thus establishing this approach as the most effective model of an immunomodulating therapy of human neoplasms. Early observations with an ongoing phase I/II study with CD16/CD30 Bi-MAb in patients with refractory Hodgkin's disease confirm the expected low toxicity. If these observations can be confirmed in larger clinical studies, effector cell activating Bi-MAbs could become an important weapon in the remaining fight for the conquest of Hodgkin's disease.