Construction of optimized bispecific antibodies for selective activation of the death receptor CD95.

Target cell-restricted triggering of the CD95 (APO-1/Fas) death receptor with bispecific antibody fragments.

Like many other cell surface receptors, the CD95 (APO-1/Fas) molecule needs to be cross-linked by its physiological ligand or by immobilized or multimeric antibodies to mediate biological activity, that is, induction of apoptotic cell death. Monomeric CD95 antibodies of the IgG2a or IgG1 subtype block rather than induce apoptosis. We report here that such antibodies, hybridized to a second anti...

Immunotherapy of B-cell lymphoma with CD3x19 bispecific antibodies: costimulation via CD28 prevents "veto" apoptosis of antibody-targeted cytotoxic T cells.

Bispecific antibodies (CD3x19) against the CD3epsilon-chain of the T-cell-receptor/CD3 complex and the CD19 antigen on B cells can target polyclonal, nontumor-specific T cells to B lymphoma cells. This induces T-cell activation, and generation of cytotoxic T cells (CTLs). These polyclonal CTLs, targeted by the CD3x19 bispecific antibodies, can lyse CD19(+) B-lymphoma cells. In a xenotransplant ...

Functional CD95 ligand and CD95 death-inducing signaling complex in activation-induced cell death and doxorubicin-induced apoptosis in leukemic T cells.

Activation-induced cell death (AICD) in T cells is mediated by CD95 ligand (CD95L)/receptor interaction, which has also been implicated in apoptosis induction by some anticancer agents. In this article we show that both anti-CD3-triggering (AICD) and doxorubicin treatment led to the production of a functionally active CD95L in the CD3+/T-cell receptor-positive (TCR+) T leukemia cell line H9. CD...

Melanoma-directed activation of apoptosis using a novel bispecific antibody directed at MCSP and TRAIL receptor 2/Death

A Comparative Investigation of the Bispecific Antibody: Expression in Expi293F Cells and E.Coli

Aims: Bispecific antibodies are capable of targeting two cell surface markers simultaneously. Blinatumomab an anti-CD3/CD19 Bispecific T cell engager antibody (BiTE) is approved for clinical application by FDA. This BiTE effectively targets malignant cells in ALL (Acute Lymphoblastic Leukemia) patients. For production of large quantities of such antibodies in industrial settings choice of host ...