CAR-T therapy: Prospects in targeting cancer stem cells

Abstract

Cancer stem cells (CSCs), a group of tumour cells with stem cell characteristics, have the ability of self-renewal, multi-lineage differentiation and tumour formation. Since CSCs are resistant to conventional radiotherapy and chemotherapy, their existence may be one of the root causes of cancer treatment failure and tumour progression. The elimination of CSCs may be effective for eventual tumour eradication. Because of the good therapeutic effects without major histocompatibility complex (MHC) restriction and the unique characteristics of CSCs, chimeric antigen receptor T-cell (CAR-T) therapy is expected to be an important method to eliminate CSCs. In this review, we have discussed the feasibility of CSCs-targeted CAR-T therapy for cancer treatment, summarized current research and clinical trials of targeting CSCs with CAR-T cells and forecasted the challenges and future direction from the perspectives of toxicity, persistence and potency, trafficking, infiltration, immunosuppressive tumour microenvironment, and tumour heterogeneity.

Keywords: CAR-T; cancer stem cells; immunotherapy; targeted therapy.

FIGURE 1

Diagram of CAR‐T treatment process. CAR‐T cell therapy can be defined as a treatment in which a patient's T cells are genetically modified in laboratory to express chimeric antigen receptors (CARs) and attack cancer cells. The process of adoptive CAR‐T cell therapy includes the following steps:(1) isolation of T cells from the peripheral blood sample by the process of leukapheresis; (2) transduction of cells by a viral vector encoding the CAR gene; (3) expansion of in vitro CAR‐T cells; (4) administration into the patient to kill cancer; (5) monitoring: observe curative effect and monitor adverse reactions