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

Int J Cancer. 2008 Sep 1;123(5):1181-9. doi: 10.1002/ijc.23626.


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 x anti-CD3), that connects B cells and T cells via its variable regions and recruits FcgammaRI(+) 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-gamma and very low IL-4 secretion. In conclusion, Bi20 may offer new immunotherapeutic options for the treatment of B-cell lymphomas.

MeSH terms

  • Animals
  • Antibodies, Bispecific / pharmacology
  • Antibodies, Bispecific / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Antigens, CD20 / immunology*
  • Antineoplastic Agents / pharmacology*
  • Burkitt Lymphoma / drug therapy
  • CD3 Complex / immunology*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Isoelectric Focusing
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukocytes, Mononuclear / drug effects
  • Lymphocyte Depletion
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Mice


  • Antibodies, Bispecific
  • Antigens, CD20
  • Antineoplastic Agents
  • Bi20 antibody
  • CD3 Complex