specifically_Blood中文时讯

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#specifically# A cellular antidote to specifically deplete anti-CD19 ...

BRIEF REPORT| FEBRUARY 13, 2020

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


Marco 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. Gill
Blood (2020) 135 (7): 505–509.
https://doi.org/10.1182/blood.2019001859

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.

Subjects:
Brief Reports, Gene Therapy, Immunobiology and Immunotherapy
Topics:
antidotes, burkitts lymphoma, cd19 antigens, chimeric antigen receptors, t-lymphocytes, leukemia, b-cell, acute,leukemia, leukemic cells, blast cells, neoplasms
This 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.


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