Alice Cho, PhD, CRI-Carson Family Fellow The Rockefeller University Area of Research: All Cancers Antibody-based therapies, which work by blocking signaling pathways or engaging early innate immune cell responses, have been widely used to treat patients with certain types of cancers, autoimmune diseases, and infectious diseases. They may also modulate adaptive immune responses, including by enhancing killer T cell responses in a process called the vaccinal effect, which may allow for long-term protection against cancer or viruses. The exact mechanisms underlying the vaccinal effect remain poorly defined though, so Dr. Cho proposes to characterize this process in a mouse model of chronic viral infection.She will first generate a panel of LCMV-targeting antibodies, both those that neutralize the virus and those that don’t, and then analyze their properties to better understand how neutralizing antibodies are generated in response to chronic viral infections. Additionally, a selection of these antibodies will be used to therapeutically treat mice with ongoing LCMV infections. In addition to therapeutically treating mice with ongoing infections, she will also evaluate how both neutralizing and non-neutralizing antibodies are able to protect chronically infected mice, and determine the extent to which LCMV-specific killer T cells are activated after antibody treatment. Overall, these results should provide important insight into how antibody therapies may be designed to further enhance the vaccinal effect and improve immune responses against a range of diseases. Projects and Grants Effect of Therapeutic Antibody Administration on Treating Chronic Viral Infections The Rockefeller University | All Cancers | 2020 | Michel C. Nussenzweig MD, PhD