Challenges of chimeric antigen receptor T-cell therapy in chronic lymphocytic leukemia: lessons learned

Ismail Can, Michelle J. Cox, Elizabeth L. Siegler, Reona Sakemura, Saad S. Kenderian

Research output: Contribution to journalReview articlepeer-review


Development of chimeric antigen receptor T cell (CART) therapy has led to an unprecedented success against B-cell leukemia and lymphoma and resulted in U.S. Food and Drug Administration–approved treatment protocols. Despite the initial clinical response in B cell–related malignancies, high relapse rates suggest that much work is needed to uncover mechanisms of resistance. In chronic lymphocytic leukemia (CLL), the durable activity of CAR T-cells is limited, and CAR T-cell therapy success is lower than in other malignancies. T cells from these patients are vulnerable to a state of dysfunction because of stresses including chronic infection, rapid cell cycle on antigen recognition, immunosuppressive tumor microenvironment, and cancer-related treatments. T cells are also introduced to additional stresses when cultured ex vivo during the CAR T-cell manufacturing process. All these factors contribute to the limited regenerative capacity of T cells, which can lead to CAR T-cell treatment failure. In this article, we review the challenges of CAR T-cell therapy in patients with CLL and discuss potential strategies to overcome these challenges.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalExperimental Hematology
StatePublished - Apr 2022

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research


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