Abstract
Chimeric antigen receptor-T cell (CAR-T) therapy has been studied intensively these years and is considered a promising cancer treatment. So far, Food and Drug Administration has approved 2 CAR-T cell therapy for patients with refractory leukemia and the result is positive. However, CAR-T cell therapy is still facing several challenges, including antigen escape, which will diminish the efficacy of treatment and lead to relapse. This review investigates the potential of cancer stem cell (CSC), a small group of cancer cells that contribute to tumorigenesis, metastasis, therapy resistance and relapse, as the target of CAR-T cell therapy, focusing on representative CSC surface markers: CD123, CD133 and CD44. Evidence indicates that CAR-T cell therapy directed by CSC surface markers is effective and feasible. Therefore, CSC targeted CAR-T cell therapy is a prospective treatment for cancer.
Highlights
Chimeric antigen receptor-T cell (CAR-T) therapy is a promising cancer treatment
Previous studies have shown that CD123, known as interleukin-3 receptor alpha chain, has been overly expressed in hematologic malignancies, including acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia and the presence of CD123 is always associated with poor prognosis
This review presents the potential of using cancer stem cell (CSC) as the target of CAR-T cell therapy and discusses CSC surface markers CD123, CD133 and CD44 directed CAR-T in detail
Summary
Chimeric antigen receptor-T cell (CAR-T) therapy is a promising cancer treatment. CAR-T cells are genetically engineered T cells consisting 3 parts: an extracellular antibody-like surface domain, a transmembrane domain and an intracellular signaling domain 1. CD123 is a cancer stem cells surface marker and the current success raises cancer stem cells, a subpopulation of tumor cells, as potential targets for CAR-T therapy because of their stem cell like characteristics and their contribute to tumorigenesis and relapse[10]. Some of the circulating tumor cells express cancer stem cell surface markers and are highly tumorigenic[14] With their multi-layers self-defense lines and the ability to rapidly repair DNA, CSCs are considerably more resistant to chemo- and radio- therapy compared with normal tumor cell and would relapse1516. These characteristics indicate that CSCs play a significant role in the development of tumor, the resistance to clinical treatment and the relapse of cancer. They imply that CSCs are useful targets for cancer therapy because once CSCs are removed, the severity of tumor would decrease remarkably
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