Define the Intersection of CARs and Oncolytic Viruses


Adoptive transferred T cells have not been shown to expand and persist in patients with solid tumors. Some of the main limitations identified in ACT applied to solid tumors include (a) poor T cell persistence within the tumor microenvironment and (b) loss of antigen expression. Our hypothesis is that combining oncolytic virus armed with immunostimulatory genes (including cytokines or BiTEs) with engineered T cells may enhance the efficacy of ACT. We propose that combination of redirected T cells with oncolytic virus have the potential to (1) cause direct tumor debulking (2) break tumor immunosupression; (3) enhance homing and persistence of T cells; and (4) kill tumor cells that may lose antigen expression.To test this hypothesis, we compared different kinds of oncolytic virus armed with immunostiumulatory genes. Oncolytic adenoviruses armed with fusogenic proteins or BiTEs against EGFR or FAP will be tested (in collaboration with Dr. Alemany, IDIBELL). Also, other oncolytic viruses as VSV or Vaccinia virus, which are highly immunogenic, were tested in combination with engineered T cells. T cells will be engineered to express a transgenic TCR targeting NY-ESO.


A manuscript entitled: “Improving CAR-T cell therapy with the Oncolytic virus-driven production of a Bispecific T-cell engager” was published in Cancer Immunol Res; 6(5); 605-16. ©2018 AACR. (


Project Participants: Carl June, Sonia Guedan-Carrio, Carolyn Shaw and Anna Wing