A cellular antidote to specifically deplete anti-CD19 chimeric antigen receptor–positive cells

• Published in: Blood Vol. 135; no. 7; pp. 505 - 509
• Main Authors: Ruella, Marco, Barrett, David M., Shestova, Olga, Perazzelli, Jessica, Posey, Avery D., Hong, Seok Jae, Kozlowski, Miroslaw, Lacey, Simon F., Melenhorst, J. Joseph, June, Carl H., Gill, Saar I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.02.2020; American Society of Hematology
• Subjects: Animals; Antigens, CD19 - immunology; Brief Report; Cytotoxicity, Immunologic; Humans; Immunobiology and Immunotherapy; Immunotherapy, Adoptive; Mice; Receptors, Chimeric Antigen - immunology; T-Lymphocytes - immunology
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2019001859

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. •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. [Display omitted]