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.
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.
Micromet AG, Staffelseestr. 2, 81477 Munich, Germany.
Sandrine
S
d'Argouges
Sandra
S
Wissing
Christian
C
Brandl
Nadja
N
Prang
Ralf
R
Lutterbuese
Alex
A
Kozhich
Joann
J
Suzich
Mathias
M
Locher
Peter
P
Kiener
Peter
P
Kufer
Robert
R
Hofmeister
Patrick A
PA
Baeuerle
Ralf C
RC
Bargou
D018033:Antibodies, Bispecific / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017252:CD3 Complex / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D053804:Granzymes; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology; D000069283:Rituximab; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D017252:CD3 Complex; D000069283:Rituximab; C510808:blinatumomab; D053804:Granzymes; D053148:Caspase 3; D053179:Caspase 7