Treatment of Heterotransplanted Hodgkin's Tumors in SCID Mice by a Combination of Human NK or T Cells and Bispecific Antibodies

摘要

To test the feasibility and efficacy of a new immunotherapeutic approach in Hodgkin's disease, bispecific monoclonal antibodies (BsmAb) were established with specificity for the Hodgkin's-associated CD30 antigen and for CD16 (on NK cells) or CD3 and CD28 (on T lymphocytes), respectively. These BsmAb induced a specific and efficient NK cell or T cell-mediated cytotoxicity in vitro. The treatment of severe combined immunodeficiency (SCID) mice with the NK (anti-CD16/CD30) or T cell (anti-CD3/CD30 and anti-CD28/CD30) activating BsmAb followed by administration of resting human lymphocytes led to complete remission of established heterotransplanted human Hodgkin's tumors. Even disseminated tumors were cured. Studies on the mechanism responsible for tumor destruction revealed that treatment efficacy depended on lymphocyte activation at the tumor site. Localization of human lymphocytes in mice was BsmAb mediated and antigen specific as activated lymphocytes were only detected in CD30+ tumors but not in CD30- colorectal carcinomas co-established as a control in the same animal.