Natural killer cells: a review of manufacturing and clinical utility

Koepsell, Scott A.; Miller, Jeffrey S.; McKenna, David H.

doi:10.1111/j.1537-2995.2012.03724.x

Cited by 77 publications

(69 citation statements)

References 42 publications

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“…NK cell therapy is applicable to various forms of cancer (85,86), but its current use has been focused primarily in hematologic malignancies (20,63,87,88). NK cells can be used for patients with refractory leukemia and can be given before conventional HCT for induction of remission, after HCT as consolidation, or in place of HCT.…”

Section: Clinical Considerationsmentioning

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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Section: Clinical Considerationsmentioning

confidence: 99%

Infusions of Allogeneic Natural Killer Cells as Cancer Therapy

Leung

2014

Clinical Cancer Research

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“…Following incubation with cytokines, particularly interleukin (IL)-2 or IL-15, NK cells acquire the capacity to lyse a broad array of fresh and cultured tumor targets not normally sensitive to NK lysis. [43][44][45][46][47][48] Another strategy is combination therapy with monoclonal antibodies to boost ADCC. [49][50][51][52][53] Functional NK cells for immunotherapy can be derived from several different sources, as demonstrated by a number of groups.…”

Section: Adoptive Transfer Of Nk Cells To Target Tumorsmentioning

confidence: 99%

“…27,31 For example, some leukemia and lymphoma cells maintain high surface expression of HLA molecules, making them invisible to NK attack, 31,32 or may lack ligands that signal through activating NK cell receptors. 31 Thus, many groups have explored strategies to enhance the activity of NK cells, including the use of cytokines and artificial antigen-presenting cells (APCs) with enhanced costimulatory molecules as feeder cells [43][44][45][46] for their in vivo expansion. Following incubation with cytokines, particularly interleukin (IL)-2 or IL-15, NK cells acquire the capacity to lyse a broad array of fresh and cultured tumor targets not normally sensitive to NK lysis.…”

Section: Adoptive Transfer Of Nk Cells To Target Tumorsmentioning

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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“…NK cells make up only approximately 10% of mononucleated cells in the blood and even less in umbilical cord blood, while the number of NK cells that can be obtained via apheresis procedure on average 1-3 × 10 7 /kg of an adult individual, enough in general for 1 transfer dose only [24,25] which makes NK cell expansion necessary. Different methods have been developed for NK expansion, both in vivo and ex vivo [25].…”

Section: Nk Cell Expansionmentioning

confidence: 99%

NK cell therapy after hematopoietic stem cell transplantation: can we improve anti-tumor effect?

Elssen

Ciurea

2017

Int J Hematol

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After decades since the discovery of natural killer (NK) cells as potential effector cells fighting malignantly transformed and virally infected cells, little progress has been made in their clinical application. This yet unrealized therapeutic effect is presumably, at least in part, due to low numbers of functional NK cells that could be obtained from the peripheral blood relative to tumor burden. Our group hypothesized that a relatively small NK cell number to targeted malignant cells is the cause of a lack of clinical effect. We pursued obtaining large numbers of NK cells via ex vivo expansion using feeder cells that express membrane-bound IL-21. Early clinical studies demonstrate safety of administration of ex vivo expanded NK cells after transplantation using this method and suggest a therapeutic benefit in terms on decreasing relapse rate and possible control of viral infections post-transplant can be achieved. Successful application of NK cells after hematopoietic stem cell transplantation opens the possibility to effectively enhance the anti-tumor effect and decrease relapse rate post-transplant. Moreover, high doses of NK cells could prove more efficacious in enhancing anti-tumor effects, not only in hematological malignancies, with our without transplantation, but also in solid tumor oncology.

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Natural killer cells: a review of manufacturing and clinical utility

Cited by 77 publications

References 42 publications

Infusions of Allogeneic Natural Killer Cells as Cancer Therapy

Infusions of Allogeneic Natural Killer Cells as Cancer Therapy

Engineering Natural Killer Cells for Cancer Immunotherapy

NK cell therapy after hematopoietic stem cell transplantation: can we improve anti-tumor effect?

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