scholarly journals Lysis of neuroblastoma cell lines by human natural killer cells activated by interleukin-2 and interleukin-12

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1323-1328 ◽  
Author(s):  
AR Rossi ◽  
F Pericle ◽  
S Rashleigh ◽  
J Janiec ◽  
JY Djeu
Keyword(s):  
Natural Killer ◽  
Cell Lines ◽  
Nk Cell ◽  
Neuroblastoma Cell ◽  
Interleukin 2 ◽  
Cell Lysis ◽  
Interleukin 12 ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells ◽  
Neuroblastoma Cell Lines

Abstract Neuroblastoma is the most common extracranial, solid tumor in children. Despite intensive chemotherapy and bone marrow transplantation, the 5- year projected survival rate is 20% to 25%. In vitro studies have shown enhanced natural killer cell (NK) lysis of tumor cells after exposure of NK cells to interleukin-2 (IL-2). In vivo studies have demonstrated similar immunologic effects but have also revealed severe toxicities associated with the use of IL-2. IL-12 is a newly described cytokine that has several properties, including the ability to act synergistically with IL-2 in generating lymphokine-activated killer cells (LAK) against known tumor targets. We investigated the role of IL- 12 in the generation of peripheral blood mononuclear cell (PBMC) lysis of neuroblastoma cell lines. PBMC were activated with IL-12 alone and in combination with IL-2. Whereas IL-12 alone produced only modest enhancement of NK cell cytotoxicity, the combination of IL-2 and IL-12 was most effective in activating NK cell lysis of neuroblastoma cell lines. Further, we showed that large granular lymphocytes were the effector cells involved in target cell lysis. Finally, the CD18 molecule was shown to be critical in the lysis of neuroblastoma cells by activated PBMC.

scholarly journals Lysis of neuroblastoma cell lines by human natural killer cells activated by interleukin-2 and interleukin-12

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1323-1328 ◽  
Author(s):  
AR Rossi ◽  
F Pericle ◽  
S Rashleigh ◽  
J Janiec ◽  
JY Djeu
Keyword(s):  
Natural Killer ◽  
Cell Lines ◽  
Nk Cell ◽  
Neuroblastoma Cell ◽  
Interleukin 2 ◽  
Cell Lysis ◽  
Interleukin 12 ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells ◽  
Neuroblastoma Cell Lines

Neuroblastoma is the most common extracranial, solid tumor in children. Despite intensive chemotherapy and bone marrow transplantation, the 5- year projected survival rate is 20% to 25%. In vitro studies have shown enhanced natural killer cell (NK) lysis of tumor cells after exposure of NK cells to interleukin-2 (IL-2). In vivo studies have demonstrated similar immunologic effects but have also revealed severe toxicities associated with the use of IL-2. IL-12 is a newly described cytokine that has several properties, including the ability to act synergistically with IL-2 in generating lymphokine-activated killer cells (LAK) against known tumor targets. We investigated the role of IL- 12 in the generation of peripheral blood mononuclear cell (PBMC) lysis of neuroblastoma cell lines. PBMC were activated with IL-12 alone and in combination with IL-2. Whereas IL-12 alone produced only modest enhancement of NK cell cytotoxicity, the combination of IL-2 and IL-12 was most effective in activating NK cell lysis of neuroblastoma cell lines. Further, we showed that large granular lymphocytes were the effector cells involved in target cell lysis. Finally, the CD18 molecule was shown to be critical in the lysis of neuroblastoma cells by activated PBMC.

Jagged2 promotes the development of natural killer cells and the establishment of functional natural killer cell lines

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3521-3527 ◽  
Author(s):  
Sarah L. DeHart ◽  
Marc J. Heikens ◽  
Schickwann Tsai
Keyword(s):  
Natural Killer Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Lines ◽  
Nk Cell ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lymphoid Cells ◽  
Killer Cells ◽  
Hematopoietic Stem

AbstractEmerging evidence indicates that Notch receptors and their ligands play important roles in the development of T cells and B cells. However, little is known about their possible roles in the development of other lymphoid cells. Here we demonstrate that Jagged2, a Notch ligand, stimulates the development of natural killer (NK) cells from Lin- Sca-1+ c-kit+ hematopoietic stem cells. Our culture system supports NK cell development for 2 to 3 months, often leading to the establishment of continuous NK cell lines. The prototype of such cell lines is designated as KIL. KIL depends on interleukin-7 for survival and proliferation and is NK1.1+ CD3- TCRαβ- TCRδγ- CD4- CD8- CD19- CD25+ CD43+ CD45+ CD49b- CD51+ CD94+ NKG2D+ Mac-1-/low B220- c-kit+ perforin I+ granzyme B+ Notch-1+, and cytotoxic. Like normal natural killer cells, the T-cell receptor-β loci of KIL remain in the germ-line configuration. In response to interleukin-2, KIL proliferates extensively (increasing cell number by approximately 1010-fold) and terminally differentiates into adherent, hypergranular NK cells. Our findings indicate that Jagged2 stimulates the development of natural killer cells and the KIL cell line preserves most properties of the normal NK precursors. As such, KIL provides a valuable model system for NK cell research.

scholarly journals Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes’ army

2019 ◽  
Vol 5 (10) ◽  
pp. FSO425
Author(s):  
Ricardo García-Muñoz ◽  
María-Josefa Nájera ◽  
Jesús Feliu ◽  
Judith Antón-Remírez ◽  
Enrique Ramalle-Gómara ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Killer Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells

Aim: To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients. Patients & methods: The distribution of peripheral blood NK cells of 31 patients was analyzed by flow cytometry. Results: We detected a decrease of NK cells in peripheral blood below normal range after obinutuzumab treatment. During maintenance treatment with subcutaneous rituximab, an NK cell reduction was less pronounced than after intravenous rituximab treatment, despite lymphokine-activated killer cell infusions. Conclusion: After one dose of obinutuzumab, each NK cell in peripheral blood destroys 25 leukemic cells.

scholarly journals Neuroblastoma Cell Lines Are Refractory to Genotoxic Drug-Mediated Induction of Ligands for NK Cell-Activating Receptors

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Irene Veneziani ◽  
Elisa Brandetti ◽  
Marzia Ognibene ◽  
Annalisa Pezzolo ◽  
Vito Pistoia ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Nk Cell ◽  
Neuroblastoma Cell ◽  
Therapeutic Interventions ◽  
Experimental Conditions ◽  
Activating Receptors ◽  
Damage Response ◽  
Differentiating Agents ◽  
Neuroblastoma Cell Lines

Neuroblastoma (NB), the most common extracranial solid tumor of childhood, causes death in almost 15% of children affected by cancer. Treatment of neuroblastoma is based on the combination of chemotherapy with other therapeutic interventions such as surgery, radiotherapy, use of differentiating agents, and immunotherapy. In particular, adoptive NK cell transfer is a new immune-therapeutic approach whose efficacy may be boosted by several anticancer agents able to induce the expression of ligands for NK cell-activating receptors, thus rendering cancer cells more susceptible to NK cell-mediated lysis. Here, we show that chemotherapeutic drugs commonly used for the treatment of NB such as cisplatin, topotecan, irinotecan, and etoposide are unable to induce the expression of activating ligands in a panel of NB cell lines. Consistently, cisplatin-treated NB cell lines were not more susceptible to NK cells than untreated cells. The refractoriness of NB cell lines to these drugs has been partially associated with the abnormal status of genes for ATM, ATR, Chk1, and Chk2, the major transducers of the DNA damage response (DDR), triggered by several anticancer agents and promoting different antitumor mechanisms including the expression of ligands for NK cell-activating receptors. Moreover, both the impaired production of reactive oxygen species (ROS) in some NB cell lines and the transient p53 stabilization in response to our genotoxic drugs under our experimental conditions could contribute to inefficient induction of activating ligands. These data suggest that further investigations, exploiting molecular strategies aimed to potentiate the NK cell-mediated immunotherapy of NB, are warranted.

Human natural killer cells: Molecular mechanisms controlling NK cell activation and tumor cell lysis

2005 ◽  
Vol 100 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Lorenzo Moretta ◽  
Cristina Bottino ◽  
Daniela Pende ◽  
Massimo Vitale ◽  
Maria Cristina Mingari ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Tumor Cell ◽  
Natural Killer ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Nk Cell ◽  
Cell Lysis ◽  
Killer Cells ◽  
Human Natural Killer Cells ◽  
Tumor Cell Lysis
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