Citations 2
Oncolytic virus–mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice
Evgin, Laura , Kottke, Tim , Tonne, Jason M., Thompson, Jill , Huff, Amanda L. , Vloten, Jacob P. van , Moore, Madelyn , Michael, Josefine, Driscoll, Christopher B. , Pulido, José S. , Swanson, Eric , Kennedy, Richard B. , Loghmani, Houra , Sánchez-Pérez, Luis, Olivier, Gloria , Harrington, Kevin J. , Pandha, Hardev , Melcher, Alan , Díaz, Rosa María, Vile, Richard G. , Tonne, Jason , van Vloten, Jacob , Driscoll, Christopher , Pulido, Jose, Kennedy, Richard , Coffey, Matt C. , Olivier, Gloria , Harrington, Kevin , Melcher, Alan A , Swanson, Eric
Science Translational Medicine | April 13, 2022 | Volume: 14 | Issue: 640 | Pages: No page available
Oncolytic viruses (OVs) encoding a variety of transgenes have been evaluated as therapeutic tools to increase the efficacy of chimeric antigen receptor (CAR)–modified T cells in the solid tumor microenvironment (TME). Here, using systemically delivered OVs and CAR T cells in immunocompetent mouse models, we have defined a mechanism by which OVs can potentiate CAR T cell efficacy against solid tumor models of melanoma and glioma. We show that stimulation of the native T cell receptor (TCR) with viral or virally encoded epitopes gives rise to enhanced proliferation, CAR-directed antitumor function, and distinct memory phenotypes. In vivo expansion of dual-specific (DS) CAR T cells was leveraged by in vitro preloading with oncolytic vesicular stomatitis virus (VSV) or reovirus, allowing for a further in vivo expansion and reactivation of T cells by homologous boosting. This treatment led to prolonged survival of mice with subcutaneous melanoma and intracranial glioma tumors. Human CD19 CAR T cells could also be expanded in vitro with TCR reactivity against viral or virally encoded antigens and was associated with greater CAR-directed cytokine production. Our data highlight the utility of combining OV and CAR T cell therapy and show that stimulation of the native TCR can be exploited to enhance CAR T cell activity and efficacy in mice.
Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay
Kennedy, Richard B. , Swanson, Eric , Watson, David , Golding, Hana , Pankratz, V. Shane , Poland, Gregory A. , Kennedy, Richard
Clinical and Vaccine Immunology | June 18, 2009 | Volume: 16 | Issue: 8 | Pages: 1105-1112
ABSTRACT Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin.