Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia. Academic Article uri icon

Overview

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.

publication date

  • October 17, 2016

Research

keywords

  • Agammaglobulinemia
  • Antigens, CD19
  • B-Lymphocytes
  • Cetuximab
  • Lymphocyte Depletion
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC5096899

Scopus Document Identifier

  • 84994560141

Digital Object Identifier (DOI)

  • 10.1182/blood-2013-03-490565

PubMed ID

  • 27760047

Additional Document Info

volume

  • 126

issue

  • 11