Objective
The general objective of this proposal is to engineer a synthetic material platform for the immobilization and delivery of a biorecognition element, that will provide an optical signal when the specific targets are engaged. This will provide a non-invasive tool to monitor the graft as a point-of-care assay allowing for patient stratification and early intervention to protect graft function.
Background Rationale
Beta-cell replacement has proven an effective approach in restoring euglycemia in type 1 diabetic patients. Despite the clinical success, grafts eventually perish due to multiple reasons, one of them being immune-mediated despite advancements in immunosuppressive regimens. While therapies that help curve the allograft immune response to overcome rejection are advancing, their activity is hampered due to their implementation at a point of no return for the cellular graft. Thus, the development of a timely and reliable diagnostic tool for graft rejection would offer a unique opportunity for early management, reducing the potential impact on the primary graft, and potentially improving graft survival and function.
Description of Project
A hurdle to the implementation of cell therapies in the clinic, despite their proven success in restoring insulin independence, is the lack of tools for non-invasive longitudinal in vivo monitoring of cell engraftment and local immune responses. Current strategies for graft monitoring have been largely limited to end-of-point, costly, and invasive approaches which can potentially destabilize cell therapy function. Herein, we aim to engineer a tool for graft monitoring that relies on the non-invasive delivery of synthetic polymeric networks for the multiplexing optical reporting of in-vivo immune responses. This engineered tool can be produced far in advance and thus provide an off-the-shelf product for personalized reporting. The lead time in monitoring the host response to the cellular therapy provided by this approach can potentially allow for the early management of host immune responses minimizing patient’s risk and improving transplant outcomes.
Anticipated Outcome
We anticipate that the early detection of specific immune signals to the beta-cell graft will allow for the timely diagnosis of changes in beta-cell graft survival and function. Specifically, we expect that we can decode a biological signature that correlates to the graft state and use non-invasive means to monitor any changes in this signature. Ultimately, allowing for the implementation of early intervention strategies to extend primary graft function.
Relevance to T1D
This project is of high relevance for the T1D community as a tool for monitoring the state of cellular therapies non-invasively will allow for external interventions to save primary graft function. We posit that preventing graft rejection of beta-cell replacement products will advance the safety of these strategies and their widespread applicability in the clinic.