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

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.