Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.
J Clin Invest
; 126(11): 4262-4272, 2016 11 01.
Article
en En
| MEDLINE
| ID: mdl-27760047
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Linfocitos T
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Depleción Linfocítica
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Antígenos CD19
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Agammaglobulinemia
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Cetuximab
Límite:
Animals
Idioma:
En
Revista:
J Clin Invest
Año:
2016
Tipo del documento:
Article