Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells

Boissel, Laurent; Betancur, Monica; Wels, Winfried S.; Tuncer, Hande H.; Klingemann, Hans

doi:10.1016/j.leukres.2008.11.024

Cited by 144 publications

(133 citation statements)

References 23 publications

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“…High transfection efficiency and a high survival rate have been reported in both NK cell lines and primary NK cells. Much higher transfection efficiency was achieved using mRNA compared to using DNA [148][149][150][151][152]. Introduction by nucleofection has also been tried, but the efficiency was not high [153,154].…”

Section: Genetic Modification-gene Transfer To Nk Cellsmentioning

confidence: 99%

Clinical Applications of Natural Killer Cells

Harada¹,

Teraishi²,

Ishii³

et al. 2017

Natural Killer Cells

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Natural killer (NK) cells are an essential component of the innate immune system, and they play a crucial role in immunity against malignancies. Recent advances in our understanding of NK cell biology have paved the way for new therapeutic strategies based on NK cells for the treatment of various cancers. In this section, we will focus on NK cell immunotherapy, including the enhancement of antibody-dependent cellular cytotoxicity, the manipulation of receptor-mediated activation, inclusion criteria based on killer cell immunoglobulin-like receptor (KIR) ligand mismatches, and adoptive immunotherapy with ex vivo expanded chimeric antigen receptor (CAR)-engineered or engager-modified NK cells. In contrast to T lymphocytes, donor NK cells do not attack any recipient tissues based on allogeneic human leukocyte antigens (HLAs), suggesting that NK-mediated antitumor effects may be achieved without the risk of graft-versus-host disease (GvHD). Despite reports of clinical efficacy, the application of NK cell immunotherapy is limited. Developing strategies for manipulating NK cell products, host factors, and tumor targets are thus current subjects of diligent study. Research into the biology of NK cells has indicated that NK cell immunotherapy has the potential to become the forefront of cancer immunotherapy in the coming years.

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Section: Genetic Modification-gene Transfer To Nk Cellsmentioning

confidence: 99%

Clinical Applications of Natural Killer Cells

Harada¹,

Teraishi²,

Ishii³

et al. 2017

Natural Killer Cells

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“…This strategy can en hance tumor recognition by primary T cells (11)(12)(13)(14) and generate specific killing of tumor target cells by NK cell lines (15)(16)(17)(18) or primary human NK cells (19)(20)(21). The aim of the present study was to investigate the potential role of genetically modified NK-92 cells in the therapeutic treatment of cancer cells expressing erbB2 (HER2/neu).…”

Section: Introductionmentioning

confidence: 99%

Specific growth inhibition of ErbB2‑expressing human breast cancer cells by genetically modified NK‑92 cells

Liu

Yang

Sun³

et al. 2014

Oncol Rep

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Abstract. The natural killer cell line NK-92 shows great cytotoxicity against various types of cancer. Several types of solid tumor cells, however, can effectively resist NK-mediated lysis by interaction of major histocompatibility complex (MHC) molecules with NK cell inhibitory receptors. To generate a eukaryotic expression vector encoding chimeric antigen receptor scFv anti-erbB2-CD28-ζ and to investigate the expression and action of this chimeric antigen receptor in cancer cells both in vitro and in vivo, NK-92 cells were genetically modified with an scFv anti-erbB2-CD28-ζ chimeric recep tor by optimized electro poration using the Amaxa Nucleofector system. The expression of the chimeric receptor was evaluated by RT-PCR and immunofluorescence. The ability of the genetically modified NK-92 cells to induce cell death in tumor targets was assessed in vitro and in vivo. The transduced NK-92-anti-erbB2 scFv-CD28-ζ cells expressing high levels of the fusion protein on the cell surface were analyzed by fluorescence-activated cell-sorting (FACS) analysis. These cells specifically enhanced the cell death of the erbB2-expressing human breast cancer cell lines MDA-MB-453 and SKBr3. Furthermore, adoptive transfer of genetically modified NK-92 cells specifically reduced tumor size and lung metastasis of nude mice bearing established MDA-MB-453 cells, and significantly enhanced the survival period of these mice. The genetically modified NK-92 cells significantly enhanced the killing of erbB2-expressing cancer and may be a novel therapeutic strategy for erbB2-expressing cancer cells.

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“…The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance [74]. NK-92 leukemia cell lines were transduced to express CARs speciic for CD19 [75] and CD20 [76] expressed on B cell malignancies and also for disialoganglioside GD2, a glycolipid expressed on neuroblastoma and various other cancer types [77].…”

Section: Car-engineered Nk Cellsmentioning

confidence: 99%

NK Cells in Cancer Immunotherapy

Addou-Klouche¹

2017

Natural Killer Cells

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Natural killer (NK) cells are crucial components of the innate immune system and play critical roles in host immunity against viral infections and cancer. NK cells' activity is controlled by the interaction of a wide range of receptors expressed on their surfaces with cell surface ligands. Opposite signals delivered by inhibitory and activating receptors tightly regulate NK cells' cytotoxicity. Natural killer cells can discriminate between normal and cancer cells. NK cells are known to directly recognize and kill malignant cells or induce apoptosis. However, tumor cells have the ability to evade those atacks.The main mechanisms involve the lack of expression or downregulation of the expression of major histocompatibility complex (MHC) class I molecules and secretion of soluble NKG2D ligands by tumor cells. Furthermore, tumors harbor a population of cancer stem cells (CSCs), which can drive tumor progression and therapeutical resistance. This chapter highlights the roles of NK cells in tumor immunosurveillance and their applications for cancer immunotherapy. NK cell biology and function as well as the role of their receptor interactions will be described. We will discuss the therapeutic applications of NK cells in cancer and NK cells targeting CSCs as a promising strategy for cancer therapy.

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Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells

Cited by 144 publications

References 23 publications

Clinical Applications of Natural Killer Cells

Clinical Applications of Natural Killer Cells

Specific growth inhibition of ErbB2‑expressing human breast cancer cells by genetically modified NK‑92 cells

NK Cells in Cancer Immunotherapy

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