Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

Journal of Hematology & Oncology

Ying Gong¹  Roel G. J. Klein Wolterink²  Gerard M. J. Bos³  Wilfred T. V. Germeraad³  Jianxiang Wang⁴ 

[1] Division of Hematology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands;Division of Hematology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands;Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal;Division of Hematology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands;CiMaas BV, Maastricht, The Netherlands;State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, 300020, Tianjin, China;National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, 300020, Tianjin, China;

关键词: Cancer immunotherapy;    Adoptive cell therapy;    Chimeric antigen receptor;    Natural killer cells;    Genetic modification;   

DOI  :  10.1186/s13045-021-01083-5

来源: Springer

【 摘 要 】

Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.

【 授权许可】

CC BY