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Review
. 2020 Dec 7;13(1):168.
doi: 10.1186/s13045-020-00998-9.

Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

Ahmet Yilmaz  1 , Hanwei Cui  1 , Michael A Caligiuri  2   3   4   5 , Jianhua Yu  6   7   8   9
Affiliations
Review

Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

Ahmet Yilmaz et al. J Hematol Oncol. .

Abstract

Natural killer (NK) cells are a critical component of the innate immune system. Chimeric antigen receptors (CARs) re-direct NK cells toward tumor cells carrying corresponding antigens, creating major opportunities in the fight against cancer. CAR NK cells have the potential for use as universal CAR cells without the need for human leukocyte antigen matching or prior exposure to tumor-associated antigens. Exciting data from recent clinical trials have renewed interest in the field of cancer immunotherapy due to the potential of CAR NK cells in the production of "off-the-shelf" anti-cancer immunotherapeutic products. Here, we provide an up-to-date comprehensive overview of the recent advancements in key areas of CAR NK cell research and identify under-investigated research areas. We summarize improvements in CAR design and structure, advantages and disadvantages of using CAR NK cells as an alternative to CAR T cell therapy, and list sources to obtain NK cells. In addition, we provide a list of tumor-associated antigens targeted by CAR NK cells and detail challenges in expanding and transducing NK cells for CAR production. We additionally discuss barriers to effective treatment and suggest solutions to improve CAR NK cell function, proliferation, persistence, therapeutic effectiveness, and safety in solid and liquid tumors.

Keywords: Cancer immunotherapy; Chimeric antigen receptor; Natural killer cells; T cells.

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Conflict of interest statement

M.A. Caligiuri and J. Yu are the co-founders of CytoImmune Therapeutics, Inc. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Representative steps in CAR NK cell manufacturing for immunotherapy, RCL/RCR replication competent lentivirus/retrovirus measured by qPCR for detection of DNA encoding a viral envelope
See this image and copyright information in PMC

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