Service Project #9: Defining the Induction and Maintenance of Myelin-Specific Tolerance in T Cells and B Cells Using Local Lymph Node Depots 

Collaborating Investigator: Christopher Jewell
Affiliation: University of Maryland College Park 
Funding Status: NIH R01AI169686
Project Period: 02/01/22-01/31/27

Summary

The goal of SP #9 is to understand and control the integration of signals in the lymph node (LN) microenvironment to enable potent, myelin-specific immunotherapies that avoid immunosuppression. This will be approached using a platform that combines direct intra-LN (i.LN.) injection with controlled-release biomaterials. Biodegradable nanoimmunomaterials from TR&D2 will be evaluated for immunomodulatory activity to further the aims by delivering synergistic agents. NIMs can modulate regulatory T cells to provide a benefit in models of multiple sclerosis (MS) and potentially other autoimmune diseases. 

Approach

Aim. NIM materials for delivery of tolerogenic signals.  This aim is based around synergy with TR&D2 Specific Aim 2.3 focused on tolerogenic NIM particles. NIM particles can enable release of combination drugs including small molecules and nucleic acids and can be administered intra-LN rather than by systemic injection. The project investigates local delivery to the LN environment, efficacy of immunomodulation at reducing neuroinflammation in a mouse model for multiple sclerosis, regulatory T cell responses, and tolerogenic B cells.  

NIMs will be synthesized as described in TR&D2 Specific Aim 2.3 and sent to UMD for evaluation and use in pursuing their goals. The ability to precisely vary NIM particle size (as described in TR&D Specific Aim 2.1) can be important to modulate the loading and release properties of the particles following intra-LN injection. Polymers, capable of encapsulating multiple in-house cargos, will also be sent to enable additional tolerogenic immunomodulatory approaches. The results of this work can further the applications (route of administration, animal models) for the NIM technology, particularly for autoimmune diseases. 

TRD