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

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...

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Published inBlood 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
LanguageEnglish
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
Online AccessGet full text
ISSN0006-4971
1528-0020
1528-0020
DOI10.1182/blood.2019001859

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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. •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]
AbstractList 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.
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.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.
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]
There is a Blood Commentary on this article in this issue. 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.
Author Ruella, Marco
Barrett, David M.
Perazzelli, Jessica
Kozlowski, Miroslaw
Shestova, Olga
Posey, Avery D.
Gill, Saar I.
Hong, Seok Jae
Lacey, Simon F.
Melenhorst, J. Joseph
June, Carl H.
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– reference: 32197269 - Blood. 2020 Feb 13;135(7):460-462. doi: 10.1182/blood.2019004172
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Snippet Unintentional transduction of B-cell acute lymphoblastic leukemia blasts during CART19 manufacturing can lead to CAR19+ leukemic cells (CARB19) that are...
There is a Blood Commentary on this article in this issue. Aberrant expression of CAR19 + in B-cell acute lymphoblastic leukemia blasts can be used as the...
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StartPage 505
SubjectTerms Animals
Antigens, CD19 - immunology
Brief Report
Cytotoxicity, Immunologic
Humans
Immunobiology and Immunotherapy
Immunotherapy, Adoptive
Mice
Receptors, Chimeric Antigen - immunology
T-Lymphocytes - immunology
Title A cellular antidote to specifically deplete anti-CD19 chimeric antigen receptor–positive cells
URI https://dx.doi.org/10.1182/blood.2019001859
https://www.ncbi.nlm.nih.gov/pubmed/31703119
https://www.proquest.com/docview/2313379575
https://pubmed.ncbi.nlm.nih.gov/PMC7019191
Volume 135
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