An inducible caspase 9 safety switch can halt cell therapy-induced autoimmune disease.
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.
de Witte
Moniek A
MA
Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.
Jorritsma
Annelies
A
Swart
Erwin
E
Straathof
Karin C
KC
de Punder
Karin
K
Haanen
John B A G
JB
Rooney
Cliona M
CM
Schumacher
Ton N M
TN
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
D053453:Caspase 9