2013 Progress Report – Executive Summary
Vision: Engineering Cells as Next Generation Therapeutic Agents
Our overall translational goal is to apply the synthetic biology approaches that our center has developed to improve cancer therapy. Our focus is applying cellular engineering methods to improve cancer-directed adoptive immunotherapy. T cells can be modified to attack tumor cells by expressing artificial chimeric antigen receptors (CARs) directed against tumor associated antigens. These cell-based therapies, although in clinical trials, are still far from ideal with respect to on- vs. off-target effects and also in the ability to control designed responses. We are using synthetic biology approaches to engineer the signaling pathways of native T cell responses and in CAR-expressing T cells, in order to tune and optimize their response behaviors (reducing basal signaling, increasing threshold of activation, improved in vivo localization/persistence, engineering pharmacological gating of responses, etc.), such that they show improved control, discrimination and activity against cancer vs. non-cancer cells. In the long term, we envision that the tools we develop to engineer T cell signaling will have utility across various therapeutic applications of adoptive immunotherapy and cell therapy, beyond cancer applications.
Primary experimental focus:
We have focused on achieving greater tumor targeting specificity and control of the T cell activation response for adoptive immunotherapy; apply synthetic signaling design concepts to in vitro testing systems and translate to in vivo animal models where cell tracking and potential therapeutic T cell responses toward tumors can be gauged.