Induction of long-lasting antitumor immunity by concomitant cell therapy with allogeneic lymphocytes and trifunctional bispecific antibody

Objective. Use of a trifunctional bispecific antibody (trAb) given concomitantly with allogeneic cell therapy to achieve an anti tumor effect without graft-vs-host disease (GVHD). Materials and Methods. A trAb-directed against murine CD3 and human epithelial cell adhesion molecule (EpCAM) (BiLu), was given alone or concomitantly with interleukin (IL)-2-activated (LAK) H-2(b) donor splenocytes to H-2(d/b) mice inoculated with murine melanoma cells transfected with human EpCAM. Results. A total of 32/38 mice treated with BiLu and LAK splenocytes, were tumor-free survivors without GVHD for > 200 days following inoculation of a 100% lethal tumor dose (5 X 10(4)). Of 28 disease-free surviving mice previously treated with LAK splenocytes and BiLu, 24 mice proved resistance to a second tumor challenge of 10(4) cells given > 210 days following the first tumor inoculation with no evidence of disease for > 150 days. In contrast, only 4 of 13 disease-free survivor mice treated with naive splenocytes and BiLu, and 5 of 10 disease-free survivor controls treated with BiLu only, resisted the second tumor challenge. Induction of antitumor immunity was more efficient and long-lasting (> 150 days) in mice previously injected with a lethal tumor cell dose of 5 X 10(4) cells than in mice previously inoculated with 5 X 10(3) tumor cells. Conclusion. Concomitantly treatment of allogeneic LAK cells and trAb-induced an efficient long-lasting antitumor immunity. Considering the documented efficacy of anti-EpCAM bispecific antibody in various metastatic cancers, clinical application of our approach may be justified in patients with minimal residual disease at high risk for tumor recurrence. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.