CAR-T therapy: Prospects in targeting cancer stem cells

J Cell Mol Med. 2021 Nov;25(21):9891-9904. doi: 10.1111/jcmm.16939. Epub 2021 Sep 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Clinical Studies as Topic
  • Disease Management
  • Genetic Engineering
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / etiology
  • Neoplasms / therapy
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Treatment Outcome

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen