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

Blood. 2020 Feb 13;135(7):505-509. doi: 10.1182/blood.2019001859.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD19 / immunology*
  • Cytotoxicity, Immunologic
  • Humans
  • Immunotherapy, Adoptive
  • Mice
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD19
  • Receptors, Chimeric Antigen