In Vitro Generation of Human NK Cells Expressing Chimeric Antigen Receptor Through Differentiation of Gene-Modified Hematopoietic Stem Cells

Lowe, Emily; Truscott, Laurel; Oliveira, Satiro N. De

doi:10.1007/978-1-4939-3684-7_20

Cited by 32 publications

(23 citation statements)

References 21 publications

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“…Currently, 9 clinical trials are ongoing to evaluate the safety and efficiency of CAR-NK cells, of which 7 trials are used for leukemia or lymphoma and 2 trials are for solid tumor. In the current preclinical study, some other NK sources are under investigation [ 95 ], such as the NK cells derived from hematopoietic progenitor cells [ 96 ] or from cord blood, and expanded in vitro with the aAPC K562-based system [ 97 ].…”

Section: Nk Cell-based Immunotherapy For Cancermentioning

confidence: 99%

Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy

Liu¹,

Chen²,

Zhang³

2018

Journal of Immunology Research

107

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Nature killer (NK) cells play a critical role in host innate and adaptive immune defense against viral infections and tumors. NK cells are enriched in liver hematopoietic cells with unique NK repertories and functions to safeguard liver cells against hepatitis virus infection or malignancy transformation. However, accumulating evidences were found that the NK cells were modulated by liver diseases and liver cancers including hepatocellular carcinoma (HCC) and showed impaired functions failing to activate the elimination of the viral-infected cells or tumor cells and were further involved in the pathogenesis of liver injury and inflammation. The full characterization of circulation and intrahepatic NK cell phenotype and function in liver disease and liver cancer has not only provided new insight into the disease pathogenesis but has also discovered new targets for developing new NK cell-based therapeutic strategies. This review will discuss and summarize the NK cell phenotypic and functional changes in liver disease and HCC, and the NK cell-based immunotherapy approaches and progresses for cancers including HCC will also be reviewed.

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Section: Nk Cell-based Immunotherapy For Cancermentioning

confidence: 99%

Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy

Liu¹,

Chen²,

Zhang³

2018

Journal of Immunology Research

107

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“…Both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be maintained indefinitely to provide an almost limitless supply of NK cells. 56,57 Lowe et al 123 recently described a protocol for the differentiation of NK cells from CD34 + human HPSCs isolated from cryopreserved CB, which were then modified to express CD19-CAR molecules. The same group also described a feeder-free protocol for the generation of gene-modified NK cells from HPSCs using insulin-like growth factor 1, which could potentially be used as a platform to express other CAR molecules.…”

Section: Alternative Sources Of Nk Cellsmentioning

confidence: 99%

Engineering Natural Killer Cells for Cancer Immunotherapy

et al. 2017

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The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification. We will discuss strategies to introduce CARs into both primary NK cells and NK cell lines in an effort to provide antigen specificity, the challenges of manufacturing engineered NK cells, and evidence supporting the effectiveness of this approach from preclinical and early-phase clinical studies using CAR-engineered NK cells. CAR-NK cells hold great promise as a novel cellular immunotherapy against refractory malignancies. Notably, NK cells can provide an "off-the-shelf" product, eliminating the need for a personalized and patient-specific product that plagues current CAR-T cell therapies. The ability to more potently direct NK cell-mediated cytotoxicity against refractory tumors through the expression of CAR is likely to contribute to the recent paradigm shift in cancer treatment.

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“…In order to improve the transduction efficiency of largely virally-resistant NK cells, polybrene, which is a cationic polymer that facilitates viral entry, is commonly used [101]. Another alternative is Retronectin-a truncated version of fibronectin-which works by colocalizing with the virus at the cell's surface [102,103]. Vectofusin-1, which is a short cationic peptide that functions as a strong transduction enhancer, was originally discovered to greatly enhance the lentiviral transduction of hematopoietic stem cells and has since been adopted in the NK cell field [104].…”

Section: Viral Transductionmentioning

confidence: 99%

You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy

Pfefferle

Huntington

2020

Cancers

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The clinical success stories of chimeric antigen receptor (CAR)-T cell therapy against B-cell malignancies have contributed to immunotherapy being at the forefront of cancer therapy today. Their success has fueled interest in improving CAR constructs, identifying additional antigens to target, and clinically evaluating them across a wide range of malignancies. However, along with the exciting potential of CAR-T therapy comes the real possibility of serious side effects. While the FDA has approved commercialized CAR-T cell therapy, challenges associated with manufacturing, costs, and related toxicities have resulted in increased attention being paid to implementing CAR technology in innate cytotoxic natural killer (NK) cells. Here, we review the current landscape of the CAR-NK field, from successful clinical implementation to outstanding challenges which remain to be addressed to deliver the full potential of this therapy to more patients.

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In Vitro Generation of Human NK Cells Expressing Chimeric Antigen Receptor Through Differentiation of Gene-Modified Hematopoietic Stem Cells

Cited by 32 publications

References 21 publications

Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy

Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy

Engineering Natural Killer Cells for Cancer Immunotherapy

You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy

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