CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression

Published in Cancer
CAR T-cells that target acute B-lineage leukemia irrespective of CD19
expression
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CD19 targeting CAR T-cells demonstrate remarkable efficacy in treating B-lineage ALL (BL-ALL). Unfortunately, up to 40% of treated patients relapse with CD19 negative disease. We observed that CD19 loss is associated with preservation of highly variable, yet targetable, expression of CD20 and/or CD22. Accordingly, we reasoned that broadening the spectrum of CD19CAR T-cells to include both CD20 and CD22 will enable them to target CD19(−) escape BL-ALL while preserving their upfront efficacy. We co-expressed individual CAR molecules on T-cells using one tricistronic transgene. TriCAR T-cells effectively killed CD19 negative leukemia cells from patients who relapsed after CD19 directed T-cell therapy, while CD19CAR T-cells were ineffective. At the subcellular level, TriCAR T-cells formed dense immune synapses with target cells, were highly-effective serial killers, and were as efficacious as CD19CAR T-cells against primary CD19 positive disease. Careful evaluation in a well-designed clinical trial would determine whether TriCAR T-cells are best suited for salvage or up-front CAR therapy.


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Cancer Biology
Life Sciences > Biological Sciences > Cancer Biology
  • Leukemia Leukemia

    This journal publishes high quality, peer reviewed research that covers all aspects of the research and treatment of leukemia and allied diseases. Topics of interest include oncogenes, growth factors, stem cells, leukemia genomics, cell cycle, signal transduction and molecular targets for therapy.