title: Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.
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.forename: Paulina J
authors.initials: PJ
authors.lastname: Paszkiewicz
authors.forename: Simon P
authors.initials: SP
authors.lastname: Fräßle
authors.forename: Shivani
authors.initials: S
authors.lastname: Srivastava
authors.forename: Daniel
authors.initials: D
authors.lastname: Sommermeyer
authors.forename: Michael
authors.initials: M
authors.lastname: Hudecek
authors.forename: Ingo
authors.initials: I
authors.lastname: Drexler
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Liu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
mesh_terms: D000361:Agammaglobulinemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000068818:Cetuximab / Q000494:pharmacology*; D005260:Female; D008212:Lymphocyte Depletion; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D018941:Antigens, CD19; C000604812:CD19 antigen, mouse; D000068818:Cetuximab