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Cordes, Nicole [Author]; Kolbe, Carolin [Author]; Lock, Dominik [Author]; Holzer, Tatjana [Author]; Althoff, Deborah [Author]; Schäfer, Daniel [Author]; Blaeschke, Franziska [Author]; Kotter, Bettina [Author]; Karitzky, Sandra [Author]; Rössig, Claudia [Author]; Cathomen, Anton [Author]; Feuchtinger, Tobias F. [Author]; Bürger, Iris [Author]; Assenmacher, Mario [Author]; Schaser, Thomas [Author]; Kaiser, Andrew [Author]

Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells

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  • Media type: E-Book; Special Print
  • Title: Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells
  • Contributor: Cordes, Nicole [Author]; Kolbe, Carolin [Author]; Lock, Dominik [Author]; Holzer, Tatjana [Author]; Althoff, Deborah [Author]; Schäfer, Daniel [Author]; Blaeschke, Franziska [Author]; Kotter, Bettina [Author]; Karitzky, Sandra [Author]; Rössig, Claudia [Author]; Cathomen, Anton [Author]; Feuchtinger, Tobias F. [Author]; Bürger, Iris [Author]; Assenmacher, Mario [Author]; Schaser, Thomas [Author]; Kaiser, Andrew [Author]
  • Published: New York, NY: Elsevier, 2021
  • Published in: Molecular therapy. Methods & clinical development ; 21 (2021), 42-53
  • Extent: 1 Online-Ressource (12 Seiten); Diagramme; Supplemental information
  • Language: English
  • DOI: 10.1016/j.omtm.2021.02.013
  • Identifier:
  • Origination:
  • Footnote:
  • Description: Abstract: Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future
  • Access State: Open Access