[HTML][HTML] Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia

PJ Paszkiewicz, SP Fräßle, S Srivastava… - The Journal of …, 2016 - Am Soc Clin Investig
PJ Paszkiewicz, SP Fräßle, S Srivastava, D Sommermeyer, M Hudecek, I Drexler…
The Journal of clinical investigation, 2016Am Soc Clin Investig
The adoptive transfer of T cells that have been genetically modified to express a CD19-
specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies.
However, the persistence of functional CD19 CAR T cells causes sustained depletion of
endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a
mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery
of normal B cells. Previously, we developed a truncated version of the epidermal growth …
The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies.
The Journal of Clinical Investigation