Abstract The Johns Hopkins Translational ImmunoEngineering NCBIB, JH-TIE, is a multidisciplinary P41 program focused on the development of tools, methods, and education for the advancement of immunoengineering. Moving forward into the next five years under a renewed grant, our efforts will span a synergistic multiscale approach, from the molecular and cellular levels to tissues, organs, and systems, driven by collaborations with the scientific and clinical communities. JH-TIE’s vision is to control the powerful, yet sometimes competing, outcomes of immunity by developing advanced technologies to engineer, direct, and ultimately control immune responses. In the initial funding period, despite pandemic-related shutdowns, we successfully established work flows between the TR&Ds and CPs/SPs, leading to a total of 54 publications, 18 of which were collaborative (between TR&Ds or between TR&Ds and CPs/SPs), and nine additional collaborative grants. Over the next five years, we will develop tools, techniques, and protocols that are broadly relevant to immune and inflammatory diseases, such as autoimmunity, infectious disease, and cancer. TR&D 1 focuses on activation mechanisms – the development of platforms that efficiently activate T cells and potentiate antigen-specific effector T cells for immunotherapy. TR&D 2 extends its strong foundation in antigen delivery with the design of nanoscale packages to safely convey immunological cargos to precise cellular targets. TR&D 3 realizes a new opportunity to engineer immune responses on the protein level via signaling cue modulation – an evolution that moves away from indirect immune control (leveraging the metabolic profile of the cell that characterized the previous version of this TR&D) to more direct control of specific cytokine interactions. Collectively, the three TR&Ds will generate tools to exquisitely and selectively control immune outcomes against heretofore intractable targets at the cellular, subcellular, and molecular levels. Additionally, these innovations may open new avenues to utilizing potent immune effectors in novel ways – maximizing our understanding of and ability to engineer immune responses. The broad applicability of these tools, techniques, and protocols will be demonstrated in models of autoimmune disease, tumor immunotherapy, and infectious disease. JH-TIE will integrate diverse disciplines, with distinct tools, methods, and expertise, to address a wide range of clinical applications. Our investigators come from Departments of Pathology, Oncology, Dermatology, Biomedical Engineering, Chemical Engineering, and Materials Science and Engineering. Our diverse interests extend to a relationship with another P41, the Resource for Molecular Imaging Agents in Precision Medicine (Martin Pomper, PI). Adding in the 15 Collaborative Projects and 11 Service Projects, JH-TIE serves as a hub and a broad research interface, providing training for scientists, students, policy makers, and the general public through our education and outreach program, and accelerating the translation of immunoengineering and cellular therapies.

Narrative Our rapidly increasing understanding of the power of immune effectors, combined with development of advanced genomic tools, has generated the new field of immunoengineering, with a promise to revolutionize treatments for infectious disease, autoimmune disorders, and cancer. However, application of these breakthroughs has been stymied by remaining knowledge gaps, inefficiencies, and operational barriers between immunologists, engineers, and other partners who could collaborate and innovate. Our goal in this renewal is to continue interfacing with bioengineers, immunologists, material scientists, and biomedical researchers to develop tools, techniques, and protocols that are broadly relevant to immune and inflammatory diseases; engage in new collaborations; provide training for graduate and post-graduate investigators; and maximize the potential of immunoengineering and immune-based therapies.