Key Points

  • Aberrant expression of CAR19+ in B-cell acute lymphoblastic leukemia blasts can be used as the target for αCAR19 T cells.

  • αCAR19 T cells also recognize CAR19+ T cells, therefore representing a potential strategy to deplete CART19 cells at long term.

Abstract

Unintentional transduction of B-cell acute lymphoblastic leukemia blasts during CART19 manufacturing can lead to CAR19+ leukemic cells (CARB19) that are resistant to CART19 killing. We developed an anti-CAR19 idiotype chimeric antigen receptor (αCAR19) to specifically recognize CAR19+ cells. αCAR19 CAR T cells efficiently lysed CARB19 cells in vitro and in a primary leukemia-derived xenograft model. We further showed that αCAR19-CART cells could be used as an “antidote” to deplete CART19 cells to reduce long-term side effects, such as B-cell aplasia.

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