Safety and Efficacy of Off-the-Shelf CD30.CAR-Modified Epstein-Barr Virus-Specific T Cells in Patients with CD30-Positive Lymphoma

The manufacture of individual patient-derived CAR T-cells is expensive, frequently unsuccessful, too time consuming to benefit acutely ill patients and difficult to scale for large numbers of patients. “Off-the-shelf” T cell products that are banked from healthy donors would improve accessibility, allow rapid treatment, and reduce costs. The major obstacles to the success of allogeneic T cells are graft-versus-host disease (GVHD) and graft rejection, mediated by host and recipient alloreactive T cells, respectively. To address GVHD, we are using allogeneic Epstein-Barr Virus-specific T cells (EBVSTs), which have not produced GVHD in more than 300 recipients. To prevent graft rejection we have expressed a chimeric antigen receptor for CD30 (CD30.CAR) in EBVSTs. CD30 will be upregulated by host alloreactive T cells when they encounter infused CD30.CAR EBVSTs. As a consequence, they will become targets for the CD30.CAR EBVSTs. Previous clinical studies (NCT02917083, NCT01555892, and NCT00062868) have shown that CD30.CAR T cells can destroy CD30+ lymphoma cells through their chimeric receptor, while EBVSTs can kill EBV+ lymphoma cells through their native TCR. Thus, once engrafted, banked CD30.CAR EBVSTs may kill both CD30+ and EBV+ lymphomas through their CAR and TCR respectively without causing GVHD.