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

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Molecular therapy. Methods & clinical development. - 21 (2021) , 42-53, ISSN: 2329-0501

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2021
• Creator: Cordes, Nicole ; Kolbe, Carolin ; Lock, Dominik ; Holzer, Tatjana ; Althoff, Deborah ; Schäfer, Daniel ; Blaeschke, Franziska ; Kotter, Bettina ; Karitzky, Sandra ; Rössig, Claudia ; Cathomen, Anton ; Feuchtinger, Tobias F. ; Bürger, Iris ; Assenmacher, Mario ; Schaser, Thomas ; Kaiser, Andrew

Further information

• DOI: 10.1016/j.omtm.2021.02.013
• URN: urn:nbn:de:bsz:25-freidok-1942991
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:54 PM CET