Interleukin-15 Enhances Cytotoxicity, Receptor Expression, and Expansion of Neonatal Natural Killer Cells in Long-Term Culture

Choi, Sunwoong S.; Chhabra, Vaninder; Nguyen, Quoc Hung; Ank, Bonnie J.; Stiehm, E. Richard; Roberts, Robert L.

doi:10.1128/cdli.11.5.879-888.2004

Cited by 33 publications

(25 citation statements)

References 53 publications

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“…The studies of IL-15 [44] or IL-15Rα [45] [20]. We and others have shown that UCB NK cells rapidly acquire cytotoxic activity after IL-15 stimulation, although this activity was still lower than correspondingly IL-15-treated APB NK cells [18,48,49]. Aberrant IL-15 signaling events may exist in CB NK cells that warrant further investigation.…”

Section: Interleukin-15 Enhances Ucb Nk Cytotoxic Functionmentioning

confidence: 98%

Cytotoxic Function of Umbilical Cord Blood Natural Killer Cells: Relevance to Adoptive Immunotherapy

Lin¹,

Kuo²

2011

Pediatric Hematology and Oncology

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Decreased graft-versus-host disease (GVHD), ease of accessibility, and sustained engraftment encourage the use of umbilical cord blood (UCB) as an alternative source to bone marrow for immune reconstitution in children with leukemia. Natural killer (NK) cells rapidly expand after stem cell transplantation and are important for regulating GVHD and providing graft-versus-leukemia (GVL) effects. This review highlights the phenotypic and functional differences between UCB NK cells and adult peripheral blood (APB) NK cells, and discusses the possible therapeutic benefit of using UCB NK cells for adoptive immunotherapy in leukemia. Alloreactive NK cells show potent cytotoxic activities against human leukocyte antigen (HLA)-nonidentical leukemic cells and reduce leukemia relapses. The higher numbers of NK progenitors in UCB makes it a convenient source for ex vivo expansion of UCB NK cells for posttransplant treatment. UCB NK cells readily respond to interleukin-15, which may greatly enhance their antitumor effect. Activation and expansion protocols for UCB NK cells are currently being developed.

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Section: Interleukin-15 Enhances Ucb Nk Cytotoxic Functionmentioning

confidence: 98%

Cytotoxic Function of Umbilical Cord Blood Natural Killer Cells: Relevance to Adoptive Immunotherapy

Lin¹,

Kuo²

2011

Pediatric Hematology and Oncology

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“…18 Further investigations might improve on this by activation with additional cytokines like IL-15, IL-18 or IL-21. 28,[32][33][34] Nevertheless those strategies require close patient monitoring to investigate the influence of the respective cytokine on the cell sub-population in peripheral blood. Very recently, we could show that IL-2-stimulated NK-DLI but not unstimulated NK-DLI promote NK cell trafficking and changes in the distribution of leukocyte sub-populations in the peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers

Stangel

Passweg

Meyer-Monard

et al. 2012

Bone Marrow Transplant

163

124

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Adoptive immunotherapy with allogeneic purified natural killer (NK) cell products might exert graft-versus-tumor alloreactivity with little risk of GVHD. In a prospective phase II study in two centers, we administered purified NK cell products to high-risk patients treated with haploidentical T-cell-depleted SCT. Sixteen patients received a total of 29 NK cell infusions on days þ 3, þ 40 and þ 100 after transplantation. Median doses (and ranges) of infused NK-and T-cells per product were 1.21 (0.3-3.8) Â 10 7 /kg and 0.03 (0.004-0.72) Â 10 5 /kg, respectively. With a median follow-up of 5.8 years 4/16 patients are alive. Cause of death was relapse in five, GVHD in three, graft failure in three, and transplant related neurotoxicity in one patient. Four patients developed acute GVHDXgrade II, all receiving a total of X0.5 Â 10 5 T cells/kg. Compared with historical controls, NK cell infusions had no apparent effect on the rates of graft failure or relapse. Adoptive transfer of allogeneic NK cells is safe and feasible, but further studies are needed to determine the optimal dose and timing of NK cell therapy. Moreover, NK cell activation/expansion may be required to attain clinical benefit, while careful consideration must be given to the number of T cells infused.

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“…Although ADCC is mediated by FcgRIII (CD16), ADCC activity did not correlate with levels of surface CD16 expression on effector NK cells. This suggests that other NK cell receptors or signals (e.g., NKp46 receptor or interleukin-15) may also be involved in ADCC activity [19,32,33]. We also found that ADCC activity did not correlate with K562 cell lysis.…”

Section: Discussionmentioning

confidence: 59%

Antibody‐Dependent Cellular Cytotoxicity Mediated by Plasma Obtained before Secondary Dengue Virus Infections: Potential Involvement in Early Control of Viral Replication

et al. 2007

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Interleukin-15 Enhances Cytotoxicity, Receptor Expression, and Expansion of Neonatal Natural Killer Cells in Long-Term Culture

Cited by 33 publications

References 53 publications

Cytotoxic Function of Umbilical Cord Blood Natural Killer Cells: Relevance to Adoptive Immunotherapy

Cytotoxic Function of Umbilical Cord Blood Natural Killer Cells: Relevance to Adoptive Immunotherapy

Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers

Antibody‐Dependent Cellular Cytotoxicity Mediated by Plasma Obtained before Secondary Dengue Virus Infections: Potential Involvement in Early Control of Viral Replication

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