Overall – Summary Research in immunology has created stunning scientific advances that have the potential to revolutionize regenerative medicine, infectious disease, autoimmune disorders, neurodegenerative disease, and cancer. Yet, innovations remain in the lab, not realizing their clinical potential. Immunologists develop therapies that focus on fundamental mechanistic biology but lack tools to optimize therapies. Engineers bring a quantitative approach and highly optimized devices and treatments, but often avoid the immune system entirely, rather than trying to harness it. A profound gap exists between engineering and immunology, one that has held back life-saving innovations from reaching the clinic. The Johns Hopkins Translational ImmunoEngineering (JH-TIE) BTRC will serve as a thought leader and collaborative hub for immunoengineering research. JH-TIE will bring together the worlds of engineering and immunology, leading the research and development of transformative cancer therapies and regenerative medicine. JH-TIE's goals include: • Develop products, techniques, and methodologies to streamline the stimulation and expansion of functional T cells to provide a greater number of therapeutic cells faster and with greater proliferative potential, including a GMP-compliant batching methodology for scale-up; • Develop new enabling technologies, techniques, and products for more effective stimulation and modification of immune cells, including via biomaterials-based gene transfer and use of novel small molecule activators and inhibitors; • Develop new biotherapeutics for cellular engineering to increase T cell efficacy in vivo, including increased robustness of cytotoxic T cells against immunosuppressive counter-effects as well as complementary technology to engineer regulatory T cells for potential use for autoimmune diseases; • Expand the reach of immunoengineering principles by offering training courses, seminars, and curricula for researchers, industrial practitioners, clinicians, and students, including a new certificate program in immunoengineering for graduate students; • Advance the field of immunoengineering by hosting conferences, short courses, and other targeted offerings; • Serve as an interface and liaison for communities of engineers, immunologists, and other stakeholders. Three Technology Research and Development (TR&D) projects that will serve as a foundation for the JH-TIE center. Each TR&D is designed to deliver a technical service platform in support of a diverse community of end users. JH-TIE will provide training and dissemination of key technologies and techniques developed to collaborators and the broader research community. Collaborative and service projects are proposed in conjunction with this effort to broaden the technologies' impact. JH-TIE will expand on standard dissemination by hosting local workshops and classes, international seminars, and web-based tutorials. The JH-TIE will lead a paradigm shift and grow the field of immunoengineering. JH-TIE will achieve this through world-class research and by broadly engaging a diverse set of stakeholders. Together, these efforts will advance the field of immunoengineering, enabling new cell-based and regenerative therapies to reach the clinic, and training a generation of new immunoengineering practitioners.

Narrative Research in immunology has led to remarkable scientific advances that have the potential to revolutionize infectious disease, autoimmune disorders, neurodegenerative disease, and cancer. Yet, innovations often remain in the lab, not realizing their full clinical potential. Immunologists develop therapies that focus on fundamental mechanistic biology but lack tools to optimize therapies. Engineers bring a quantitative approach and highly optimized devices and treatments. This has resulted in a profound gap between engineering and immunology, one that has held back life-saving innovations from reaching the clinic. The Johns Hopkins Translational ImmunoEngineering (JH-TIE) BTRC will serve as a thought leader and collaborative hub for immunoengineering research. JH-TIE will bring together the worlds of engineering and immunology, leading the research and development of transformative therapies. As these studies will impact on several different disease processes including cancer and inflammatory diseases this work is consistent with NIH’s mission to improve healthcare and will impact on broadly on public health.