title: An inducible caspase 9 safety switch can halt cell therapy-induced autoimmune disease.
abstract: Transfer of either allogeneic or genetically modified T cells as a therapy for malignancies can be accompanied by T cell-mediated tissue destruction. The introduction of an efficient "safety switch" can potentially be used to control the survival of adoptively transferred cell populations and as such reduce the risk of severe graft-vs-host disease. In this study, we have tested the value of an inducible caspase 9-based safety switch to halt an ongoing immune attack in a murine model for cell therapy-induced type I diabetes. The data obtained in this model indicate that self-reactive T cells expressing this conditional safety switch show unimpaired lymphopenia- and vaccine-induced proliferation and effector function in vivo, but can be specifically and rapidly eliminated upon triggering. These data provide strong support for the evaluation of this conditional safety switch in clinical trials of adoptive cell therapy.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.
authors.forename: Moniek A
authors.initials: MA
authors.lastname: de Witte
authors.forename: Annelies
authors.initials: A
authors.lastname: Jorritsma
authors.forename: Erwin
authors.initials: E
authors.lastname: Swart
authors.forename: Karin C
authors.initials: KC
authors.lastname: Straathof
authors.forename: Karin
authors.initials: K
authors.lastname: de Punder
authors.forename: John B A G
authors.initials: JB
authors.lastname: Haanen
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Ton N M
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D019264:Adoptive Transfer / Q000009:adverse effects*; D000818:Animals; D053453:Caspase 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology
chemical_list: D053453:Caspase 9