BRIEF REPORT| FEBRUARY 13, 2020
A cellular antidote to specifically deplete anti-CD19 chimeric antigen receptor–positive cellsMarco Ruella , David M. Barrett , Olga Shestova , Jessica Perazzelli , Avery D. Posey, Jr , Seok Jae Hong , Miroslaw Kozlowski , Simon F. Lacey , J. Joseph Melenhorst , Carl H. June , Saar I. GillBlood (2020) 135 (7): 505–509.https://doi.org/10.1182/blood.2019001859
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.
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.
Immunobiology and ImmunotherapyTopics:
chimeric antigen receptors,
leukemia, b-cell, acute,
neoplasmsThis program is developed by Focus Insight with the permission of American Society of Hematology, Inc. The content are excerpted from the journal Blood. Copyright ? 2019 The American Society of Hematology. All rights reserved. “American Society of Hematology”, “ASH” and the ASH Logo are registered trademarks of the American Society of Hematology.