Bi20 (fBTA05), a novel trifunctional bispecific antibody (anti‐CD20 × anti‐CD3), mediates efficient killing of B‐cell lymphoma cells even with very low CD20 expression levels

Abstract Trifunctional bispecific antibodies can efficiently mediate tumor cell killing by redirecting T cells and immune accessory cells to the tumor cell. Here, we describe the new trifunctional antibody, Bi20 (FBTA05, anti‐CD20 × anti‐CD3), that connects B cells and T cells via its variable regions and recruits FcγRI + accessory immune cells via its Fc region. Bi20 mediated efficient and specific lysis of B‐cell lines and of B cells with low CD20 expression levels that were derived from CLL patients. Remarkably, T‐cell activation and tumor cell killing occurred in an entirely autologous setting without additional effector cells in 5 of 8 samples. In comparison, rituximab, a chimeric monoclonal CD20 antibody, demonstrated a significantly lower B‐cell eradication rate. Additionally, Bi20, but not rituximab, upregulated the activation markers CD25 and CD69 on both CD4 + and CD8 + T cells in the presence of accessory immune cells. CD14 + accessory cells and the monocyte cell line THP‐1 were activated via binding of the Fc region of Bi20, given that T cells were simultaneously engaged by the antibody. Bi20 induced a strong Th1 cytokine pattern characterized by high IFN‐γ and very low IL‐4 secretion. In conclusion, Bi20 may offer new immunotherapeutic options for the treatment of B‐cell lymphomas. © 2008 Wiley‐Liss, Inc.