03.26.21

CAR T-cells targeting B-linage ALL irrespective of CD-19

The following content was featured in a recent Abstracts newsletter distributed by ASTCT. The Abstracts newsletter highlights the latest research in the clinical research and translational science studies aspects of transplantation and cellular therapy. 

Fousek K, Watanabe J, Joseph SK, et al. CAR T-Cells That Target Acute B-Lineage Leukemia Irrespective of CD19 Expression. Leukemia. 2021; (doi: 10.1038/s41375-020-0792-2).

Evidence shows that chimeric antigen receptor (CAR) T-cells targeting CD20 or CD22 represent a viable upfront or rescue therapy in patients with B-lineage acute lymphoblastic leukemia. The focus until now has been on CD19, which is expressed in virtually all cases. Despite a high level of success, nearly 40% of treated patients ultimately relapse due to CD19(-) escape. Investigators suspected that CD20 and CD22, alternative markers of B-cell malignancies, might also represent valid targets for CAR T-cell therapy. The antigens are present in 50% and 80–90% of cases, respectively. Although they are downregulated by CD19(-) escape, their surface expression is preserved to some extent. The researchers developed a CAR T-cell with the capacity to target not only CD19 but CD20 and CD22 at the same time. The intervention killed CD19(-) blasts from patients who experienced relapse following CD19 CAR T-cell treatment. Cytolytic activity with CD19/20/22 CAR T-cells was superior to that of CD19 CAR T-cells, and the therapy worked just as well as CD19 CAR T-cells against primary CD19-expressing disease. Moreover, CD19/20/22 CAR therapy achieved a result the CD19 CAR therapy could not: controlling growth of CD19(-) leukemia cells in patients who failed CD19 CAR therapy.

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