BISPECIFIC ANTIBODY TREATMENT OF MURINE B-CELL LYMPHOMA

This report summarizes our experimental data concerning the use of bis pecific antibodies (bsAb) for the treatment of the murine BCL1 B cell lymphoma model. Initially we used a hybrid-hybridoma-derived bsAb with specificity for the TcR/CD3 complex on T cells and the idiotype of th e membrane-bound IgM on the tumor cells. The bsAb used as a single age nt could cure animals with a low tumor load (resembling minimal residu al disease). However, in experiments aimed at increasing the therapeut ic effect in animals with a higher tumor burden, we could demonstrate the importance of additional T-cell-costimulatory signals and the care ful timing of the bsAb administration. Recently we have generated a bi specific single-chain Fv (bsscFv) fusion protein with the same dual sp ecificity as the hybrid-hybridoma-derived bsAb. Immunotherapy with thi s smaller molecule also resulted in tumor elimination in BCL1-bearing mice. A second bsscFv (alpha-CD19x alpha-CD3) with a broader applicabi lity is now being characterized and tested in vivo.