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.
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.
TRION Research GmbH, Martinsried, Germany.
Michael
M
Stanglmaier
Margot
M
Faltin
Peter
P
Ruf
Annette
A
Bodenhausen
Petra
P
Schröder
Horst
H
Lindhofer
D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000188:drug therapy; D017252:CD3 Complex / Q000276:immunology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D007525:Isoelectric Focusing; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D051379:Mice
D018033:Antibodies, Bispecific; D018951:Antigens, CD20; D000970:Antineoplastic Agents; C530113:Bi20 antibody; D017252:CD3 Complex