CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies

Marofi F., Saleh M.M., Rahman H.S., Suksatan W., Al-Gazally M.E., Abdelbasset W.K., Thangavelu L., Yumashev A.V., Hassanzadeh A., Yazdanifar M., Motavalli R., Pathak Y., Naimi A., Baradaran B., Nikoo M., Khiavi F.M.

Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biophysics, College of Applied Science, University of Anbar, Ramadi, Iraq; College of Medicine, University of Sulaimani, Sulaymaniyah, Iraq; Department of Medical Laboratory Sciences, Komar University of Science and Technology, Chaq-Chaq Qularaise, Sulaimaniyah, Iraq; Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, 10210, Thailand; College of Medicine, Al-Ameed University, Karbala, Iraq; Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia; Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt; Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Sechenov First Moscow State Medical University, Moscow, Russian Federation; Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, United States; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Professor and Associate Dean for Faculty Affairs, Taneja College of Pharmacy, University of South Florida, Tampa, FL, United States; Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia; Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran; Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Virology, Pasteur Institute of Iran, Tehran, Iran


Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR’s potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies. © 2021, The Author(s).

Chimeric antigen receptor (CAR); Hematological malignancies; Immunotherapy; Natural killer (NK) cells


Stem Cell Research and Therapy

Publisher: BioMed Central Ltd

Volume 12, Issue 1, Art No 374, Page – , Page Count

Journal Link:

doi: 10.1186/s13287-021-02462-y

Issn: 17576512

Type: All Open Access, Gold, Green


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