A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies

Shimasaki, Noriko; Fujisaki, Hiroyuki; Cho, Duck; Masselli, Marika; Lockey, Timothy; Eldridge, Paul W.; Leung, Wing; Campana, Dario

doi:10.3109/14653249.2012.671519

Cited by 153 publications

(121 citation statements)

References 38 publications

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“…Expansion of human NK cells in large numbers ex vivo is feasible 28,41 ; robust, large-scale methods for this purpose have been established 9,10 and are being used in clinical trials. Genetic modification of NK cells by retroviral transduction 28 or electroporation 42 is also possible. Therefore, the translation of the approach described here into clinical-grade conditions is realistic, and it is warranted by the predicted superior expansion and cytotoxicity of mbIL15-NK cells, particularly when burrowing into a microenvironment that may be relatively cytokinedepleted, such as the bone marrow or that adjacent to a tumor.…”

Section: Discussionmentioning

confidence: 99%

Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-15

Imamura

Shook

Kamiya

et al. 2014

Blood

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142

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Section: Discussionmentioning

confidence: 99%

Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-15

Imamura

Shook

Kamiya

et al. 2014

Blood

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142

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“…Shimasaki et al used a novel method of electroporation to introduce anti-CD19-4 -1BBL-CD3 mRNA into nonexpanded and expanded NK cells, obtaining efficiencies of 40.3% and 61.3%, respectively, and have optimized this method for future clinical application. 75 CARs specific for antigens expressed on B-cell malignancies such as CD19 and CD20, HER2/ErbB2GD2 on breast tumors, and GD2 on neuroblastoma tumors, when transduced into primary or expanded NK cells, have been shown to overcome tumor resistance to killing by autologous NK cells. These data, as well as recent data showing the efficacy of T-cell-based CAR therapy targeting CD19 in B-cell malignancies, suggest that NK cells modified to express CARs after mRNA or viral transduction represent a therapeutic tool worthy of exploration in the clinical setting.…”

Section: Future Directions: Engineering a Better Nk Cellmentioning

confidence: 99%

Bringing natural killer cells to the clinic: ex vivo manipulation

Childs

Berg

2013

Hematology

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Recently, there has been a substantial gain in our understanding of the role that natural killer (NK) cells play in mediating innate host immune responses against viruses and cancer. Although NK cells have long been known to be capable of killing cancer cells independently of antigen recognition, the full therapeutic potential of NK cell-based immunotherapy has yet to be realized. Here we review novel methods to activate and expand human NK cells ex vivo for adoptive transfer in humans, focusing on the important phenotypic and functional differences observed among freshly isolated, cytokine activated, and ex vivo-expanded NK populations. Natural killer cell therapy for cancer: a new hopeThe ability of natural killer (NK) cells to kill tumor cells without the need to recognize a tumor-specific antigen provides advantages over T cells and makes them appealing for investigation as effectors for immunotherapy. 1,2 There has recently been a substantial gain in our understanding of the role that NK cells play in mediating innate host immune responses against viruses and cancer. Although NK cells have long been known to be capable of killing cancer cells independently of antigen recognition, the full therapeutic potential of NK cell-based immunotherapy has yet to be realized. Here we review novel methods to activate and expand human NK cells ex vivo for adoptive transfer in humans, focusing on the important phenotypic and functional differences observed among freshly isolated, cytokine activated, and ex vivo-expanded NK populations. Ex vivo NK cell activation and expansionUnlike T cells, NK cells represent only a minor fraction of human lymphocytes. NK cells are defined by their CD3 Ϫ /CD56 ϩ phenotype, comprising 5% to 15% of circulating lymphocytes, and are commonly divided into CD56 dim CD16 ϩ (90%) and CD56 bright CD16 Ϫ (10%) subpopulations with distinct effector functions. Recently, investigators have shown that NK cell tumor cytotoxicity can be enhanced by disrupting NK cell signaling through inhibitory receptors such as KIR, PD-1, and NKG2A. 3,4 Furthermore, exposing tumors to drugs that down-regulate ligands for NK cell inhibitory receptors or up-regulate death receptors for NK cell effector molecules or ligands that bind NK cell-activating receptors can be used as a strategy to sensitize tumors to NK cell-mediated apoptosis. Recently, anti-PD-1 and anti-PD-L1 monoclonal antibodies and the immunomodulatory drug lenalidomide were shown to enhance both NK cell tumor trafficking and NK cell-mediated antibody-dependent cell-mediated cytotoxicity, and cytokine release against tumors while simultaneously suppressing regulatory T cell function. [5][6][7][8] Similarly, anti-CTLA-4 monoclonal antibodies have been shown to augment NK cell antibody-dependent cellmediated cytotoxicity and TNF␣ release against melanoma cells by Fc␥RIII (CD16) binding to antibody-bound tumor cells, as well as through regulatory T cell inactivation. 9-11 These data suggest these agents could be used in conjunction with autologous NK cell inf...

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“…Receptor insertion can be mediated using retroviral, lentiviral, mRNA, or Sleeping Beauty transposon/transposase systems (49)(50)(51). Investigations have shown that NK cells transduced with anti-CD19 CAR or NKG2D are potent against B-lineage and osteosarcoma cells in vivo and in vitro (49,52).…”

Section: Nk Cell Bioprocessing Ex Vivomentioning

confidence: 99%

Infusions of Allogeneic Natural Killer Cells as Cancer Therapy

Leung

2014

Clinical Cancer Research

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Natural killer (NK) cells are normal white blood cells capable of killing malignant cells without prior sensitization. Allogeneic NK cell infusions are attractive for cancer therapy because of non-cross-resistant mechanisms of action and minimal overlapping toxicities with standard cancer treatments. Although NK therapy is promising, many obstacles will need to be overcome, including insufficient cell numbers, failure of homing to tumor sites, effector dysfunction, exhaustion, and tumor cell evasion. Capitalizing on the wealth of knowledge generated by recent NK cell biology studies and the advancements in biotechnology, substantial progress has been made recently in improving therapeutic efficiency and reducing side effects. A multipronged strategy is essential, including immunogenetic-based donor selection, refined NK cell bioprocessing, and novel augmentation techniques, to improve NK function and to reduce tumor resistance. Although data from clinical trials are currently limited primarily to hematologic malignancies, broader applications to a wide spectrum of adult and pediatric cancers are under way. The unique properties of human NK cells open up a new arena of novel cell-based immunotherapy against cancers that are resistant to contemporary therapies. Clin Cancer Res; 20(13); 3390-400. Ó2014 AACR.

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A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies

Cited by 153 publications

References 38 publications

Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-15

Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-15

Bringing natural killer cells to the clinic: ex vivo manipulation

Infusions of Allogeneic Natural Killer Cells as Cancer Therapy

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