Work

Generation and validation of CRISPR-engineered human natural killer cell lines for research and therapeutic applications

Year: 2021

Type: article

Abstract: Cytotoxic natural killer cells kill tumors and infected cells. We carried out CRISPR-based gene editing and transcriptional regulation in hard-to-manipulate NK-92 cells. NK-92-based therapies were found to be safe and efficacious in preclinical studies of cancers. Here, we have pioneered the generation and validation of NK-92 cells constitutively expressing Cas9 or dCas9 for knockout (CRISPRko), transcriptional activation (CRISPRa), or transcriptional repression (CRISPRi) of genes. Our CRISPR-engineered NK-92 cell platforms can be modified for research and off-the-shelf therapeutic applications.

Source: STAR Protocols

DOI: 10.1016/j.xpro.2021.100874

Authors: Anil Kumar, Sung June Lee, Qiao Liu, Anthony K.N. Chan, Sheela Pangeni Pokharel, Jianhua Yu, Chun-Wei Chen, Srividya Swaminathan

Institutions: City Of Hope National Medical Center, City of Hope, Beckman Research Institute

Language: English

Topic: Immune Cell Function and Interaction

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,500

Funders: American Society of Hematology, Alex's Lemonade Stand Foundation for Childhood Cancer, Pharmaceutical Research and Manufacturers of America Foundation, Leukemia and Lymphoma Society, Beckman Research Institute, City of Hope, Cancer Research UK, National Institutes of Health, Stand Up To Cancer, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke

Awards: G106624557, G2201084529, G3218818806, G3366422719, G3896544870, G3968062548, G5387521688, Targeting p38 gamma signaling to advance Cutaneous T Cell Lymphoma Therapy, G5740482800, G5975785334, G6786497807, G7150943937, Experimental and preclinical modeling of NUP98-rearranged acute leukemia, G8014485703, Role of BAZ2A in MLL-r leukemia and therapeutic response, G8736805159, Characterizing and Targeting the Novel IL-15- AKT-XBP1s Pathway in NK Cells, G9000003205, G9000153559, G9000170878, G9000189708, G9000311083, G9000324369, Targeting FLT3 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Phase 1 Evaluation of Enhanced Natural Killer Cells as a Treatment Strategy in Non-Small cell Lung Cancer Patients Refractory to PD-1/PD-L1 Immune Checkpoint Inhibitors, Circumventing Barriers to Effective Oncolytic Virotherapy of Malignant Gliomas, G981769460

OpenAlex ID: W3208397947

FWCI: 0.447

Cites: 43

Cited by: 7

Related to: 10