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Outlook for New CAR-Based Therapies with a Focus on CAR NK Cells: What Lies Beyond CAR-Engineered T Cells in the Race against Cancer

May Daher and Katayoun Rezvani
May Daher
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Katayoun Rezvani
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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  • For correspondence: KRezvani@mdanderson.org
DOI: 10.1158/2159-8290.CD-20-0556 Published January 2021
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Abstract

Chimeric antigen receptor (CAR) engineering of T cells has revolutionized the field of cellular therapy for the treatment of cancer. Despite this success, autologous CAR-T cells have recognized limitations that have led to the investigation of other immune effector cells as candidates for CAR modification. Recently, natural killer (NK) cells have emerged as safe and effective platforms for CAR engineering. In this article, we review the advantages, challenges, and preclinical and clinical research advances in CAR NK cell engineering for cancer immunotherapy. We also briefly consider the feasibility and potential benefits of applying other immune effector cells as vehicles for CAR expression.

Significance: CAR engineering can redirect the specificity of immune effector cells, converting them to a much more potent weapon to combat cancer cells. Expanding this strategy to immune effectors beyond conventional T lymphocytes could overcome some of the limitations of CAR T cells, paving the way for safer and more effective off-the-shelf cellular therapy products.

Footnotes

  • Cancer Discov 2021;11:45–58

  • Received April 29, 2020.
  • Revision received July 15, 2020.
  • Accepted September 1, 2020.
  • Published first December 4, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Discovery: 11 (1)
January 2021
Volume 11, Issue 1
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Outlook for New CAR-Based Therapies with a Focus on CAR NK Cells: What Lies Beyond CAR-Engineered T Cells in the Race against Cancer
May Daher and Katayoun Rezvani
Cancer Discov January 1 2021 (11) (1) 45-58; DOI: 10.1158/2159-8290.CD-20-0556

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Outlook for New CAR-Based Therapies with a Focus on CAR NK Cells: What Lies Beyond CAR-Engineered T Cells in the Race against Cancer
May Daher and Katayoun Rezvani
Cancer Discov January 1 2021 (11) (1) 45-58; DOI: 10.1158/2159-8290.CD-20-0556
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    • Abstract
    • Introduction
    • CAR NK Cells in Cancer Therapy
    • Safety Features of CAR NK Cells
    • Challenges Facing CAR NK-Cell Therapy
    • Evolution of CAR NK-Cell Therapy
    • Alternative Cell Types for CAR Expression
    • The Next Frontier: Off-The-Shelf Cellular Therapy for Patients with Cancer
    • Conclusions and Future Prospects
    • Disclosure of Potential Conflicts of Interest
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