Oncolytic virus–mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice

Laura Evgin, Tim Kottke, Jason Tonne, Jill Thompson, Amanda L. Huff, Jacob van Vloten, Madelyn Moore, Josefine Michael, Christopher Driscoll, Jose Pulido, Eric Swanson, Richard Kennedy, Matt Coffey, Houra Loghmani, Luis Sanchez-Perez, Gloria Olivier, Kevin Harrington, Hardev Pandha, Alan Melcher, Rosa Maria DiazRichard G. Vile

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbereabn2231
JournalScience translational medicine
Issue number640
StatePublished - Apr 13 2022

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Oncolytic virus–mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice'. Together they form a unique fingerprint.

Cite this