INTRODUCTION

Many treatments for inflammatory or autoimmune disorders cause systemic immunosuppression, leading to severe and chronic toxicities. If immunity could be suppressed locally, only in targeted tissues or transplants, this could provide a way to overcome these systemic toxicities to treat diverse inflammatory diseases.

CONCLUSION

These results demonstrate that it is feasible to engineer bespoke synthetic suppressor T cells that generate locally targeted immune suppression, such as locally blocking CAR T cell attack. These engineered suppressor T cells could be tailored to generate targeted immune suppression in diverse disease contexts, including cancer NOT gates (protection of cross-reactive normal tissues), transplant rejection, and autoimmune disease. Synthetic reconstitution of complex immune signaling allows us to dissect the molecular requirements for immune suppression and design effective therapeutic cell programs.