Combination of rituximab with blinatumomab (MT103/MEDI-538), a T cell-engaging CD19-/CD3-bispecific antibody, for highly efficient lysis of human B lymphoma cells.

Abstract

We have compared the cytotoxic activity of rituximab with that of blinatumomab (MT103/MEDI-538), a single-chain CD19-/CD3-bispecific antibody engaging human T cells. Blinatumomab consistently led to a higher degree of lysis of human lymphoma lines than rituximab, and was active at much lower concentration. The cytotoxicity mediated by blinatumomab and rituximab both caused a potent activation of pro-caspases 3 and 7 in target cells, a key event in induction of granzyme-mediated apoptotic cell death. Combination of rituximab with blinatumomab was found to greatly enhance the activity of rituximab, in particular at low effector-to-target cell ratios and at low antibody concentration.

• Authors: Sandrine d'Argouges, Sandra Wissing, Christian Brandl, Nadja Prang, Ralf Lutterbuese, Alex Kozhich, Joann Suzich, Mathias Locher, Peter Kiener, Peter Kufer, Robert Hofmeister, Patrick A Baeuerle, Ralf C Bargou
• Journal: Leukemia research (Leuk Res) Vol. 33 Issue 3 Pg. 465-73 (Mar 2009) ISSN: 1873-5835 [Electronic] England
• PMID: 18835037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bispecific
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD19
• CD3 Complex
• Rituximab
• blinatumomab
• Granzymes
• Caspase 3
• Caspase 7

Topics

• Antibodies, Bispecific (pharmacology)
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD19 (immunology)
• Antineoplastic Combined Chemotherapy Protocols
• CD3 Complex (immunology)
• Caspase 3 (metabolism)
• Caspase 7 (metabolism)
• Cytotoxicity, Immunologic (drug effects)
• Drug Synergism
• Granzymes
• Humans
• Lymphoma, B-Cell (drug therapy, pathology)
• Rituximab
• Tumor Cells, Cultured