Immunology Research Program (Program 2)

ABSTRACT The Immunology (IM) program is devoted to enhancing our understanding of the function of the innate and adaptive immune system in the pathogenesis of malignant disease. There are three broad themes in the program?(1) innate immunity and the role of checkpoint innate sensors in the initiation of malignant disease; (2) adaptive immunity and the role of effector and regulatory T cells and B cells in the biology of malignant disease and graft-versus-host disease (GVHD); and (3) tumor vaccines and translational immunotherapy. The last theme focuses on nanoparticle delivery and vaccine development and a new area using modified T cells for adoptive cellular therapy. Significant highlights of the program have been seminal discoveries regarding the negative immunoregulatory role of innate sensing proteins and their role in cancer development, the generation of a novel mouse model to investigate viral induced carcinogenesis in the liver, completion of the largest clinical trial combining an antibody and tumor vaccine approach given with chemotherapy for the treatment of women with metastatic breast cancer and novel findings regarding the function of immunosuppressive pathways and immune cells in the growth of solid tumors. The third programmatic area, translational immunotherapy, is greatly enhanced by the building in 2015 of the sole cellular expansion GMP facility in the state of North Carolina and plans for genetically modified autologous T cell infusions for the treatment of patients with acute lymphoblastic leukemia, multiple myeloma and Hodgkin lymphoma in 2016. Five high profile recruits, including three junior faculty members, Edward Miao PhD, Maureen Su MD PhD, and Yuliya Pylayeva-Gupta PhD, and two senior recruits from the Cell and Gene Therapy Program at Baylor University of Medicine, Gianpietro Dotti MD and Barbara Savoldo MD PhD have joined the program since the last submission. The program is led by Jenny Ting PhD Kenan Professor of Genetics and the leader of the Translational Immunology Center at the University of North Carolina who is a world's expert on the function of proteins that mediate innate immune responses, and Jonathan Serody MD Thomas Professor of Medicine, Microbiology and Immunology and the Associate Director for Translational Sciences in the Cancer Center who is an expert on the biology of GVHD and tumor vaccines and the tumor microenvironment. There are 19 program members from five different departments in the Medical School. During the last funding period, program members have published 406 cancer-related articles (28% collaborative). In 2014, our program members held 58 grants and $17.7M (total cost) in annual extramural funding, including 6 grants and $1.7M (total costs) from the NCI.