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Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia
Paulina J. Paszkiewicz, … , Stanley R. Riddell, Dirk H. Busch
Paulina J. Paszkiewicz, … , Stanley R. Riddell, Dirk H. Busch
Published October 17, 2016
Citation Information: J Clin Invest. 2016;126(11):4262-4272. https://doi.org/10.1172/JCI84813.
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Research Article Immunology

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

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Abstract

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.

Authors

Paulina J. Paszkiewicz, Simon P. Fräßle, Shivani Srivastava, Daniel Sommermeyer, Michael Hudecek, Ingo Drexler, Michel Sadelain, Lingfeng Liu, Michael C. Jensen, Stanley R. Riddell, Dirk H. Busch

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