Key Points

  • Aberrant expression of CAR19+ in B-ALL blasts can be used as the target for anti-CAR19 chimeric antigen receptor (αCAR19) T cells

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

Unintentional transduction of B-ALL cells during CART19 manufacturing can lead to CAR19+ leukemic cells (CARB19) that are resistant to CART19. 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 furthermore demonstrated that αCAR19-CART cells could be used as an "antidote" to deplete CART19 cells to reduce long-term side effects.

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