Death Signalobody: Inducing Conditional Cell Death in Response to a Specific Antigen

Abstract

As the possibility of tumorigenesis and undesirable immune responses in patients cannot be completely excluded in gene and cell therapies, a conditional death switch to eliminate the therapeutic cells would be a valuable tool to enhance the safety of these therapies. A few ligand–receptor conditional death switches have already been developed; however, they cannot be used if patients exhibit side effects upon administration of the ligand. Here we demonstrate a death-inducing chimeric antibody named “death signalobody,” in which the antigen–antibody system, having virtually infinite ligand–receptor combinations, is utilized for the activation of death signaling. We designed a death signalobody named “SFas,” which has an antifluorescein single-chain variable fragment and the cytoplasmic domain of Fas. SFas efficiently induced conditional apoptosis in murine pro-B Ba/F3 cells in response to fluorescein-conjugated bovine serum albumin. Moreover, SFas was also able to induce antigen-dependent conditional apoptosis in human cancer cell lines. The death signalobody technique will be a valuable tool for the conditional elimination of cells of interest in multiple therapeutic applications.

Tone and colleagues describe a novel death signalobody called “SFas,” which has an antifluorescein single-chain variable fragment and the cytoplasmic domain of Fas. They show that SFas can induce antigen-dependent conditional apoptosis in human cancer cell lines. The authors suggest that this approach may allow for the conditional elimination of cells of interest in multiple therapeutic applications.