TY - JOUR
T1 - Challenges of chimeric antigen receptor T-cell therapy in chronic lymphocytic leukemia
T2 - lessons learned
AU - Can, Ismail
AU - Cox, Michelle J.
AU - Siegler, Elizabeth L.
AU - Sakemura, Reona
AU - Kenderian, Saad S.
N1 - Publisher Copyright:
© 2022
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.exphem.2022.02.001
DO - 10.1016/j.exphem.2022.02.001
M3 - Review article
C2 - 35150777
AN - SCOPUS:85126817260
SN - 0301-472X
VL - 108
SP - 1
EP - 7
JO - Experimental Hematology
JF - Experimental Hematology
ER -