Application Of Natural Killer Cells Research Articles

Advancements in the Therapeutic Application of Natural Killer Cells in Acute Myeloid Leukemia

Advancements in the Therapeutic Application of Natural Killer Cells in Acute Myeloid Leukemia

Application of Natural Killer Cells in Cancer Treatment and Its Clinical Progress

One type of effector lymphocyte that is crucial to the innate immunity is the natural killer (NK) cell. With the increasing interests in immunotherapy, the value of NK cells utilization on treating cancers is gradually being recognized and thus is transforming to be proved by current clinical trials. NK-based cancer immunotherapy results in unique cytotoxic functions in a more direct and straightforward manner which targets both hematologic cancers as well as solid tumors. Concurrently, several clinical obstacles are encountered, including immunological escape, hardship of tumor access, and effector cell fratricide, which all await to be solved and require further studies on promoting the effectiveness while remaining immuno-safety. Pleasantly, multitudinous corresponding solutions are flourishing, and researchers are using their best endeavors to accelerate positive progress in NK-based immunotherapy. Believing in a promising future of NK-related cancer immunotherapy, this review will concentrate on NK cells’ effector functions towards cancers, including the cellular mechanisms, present experimental progresses, and challenges which need to be addressed.

NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy.

Cervical cancer is one of the most prevalent gynaecological malignancies worldwide and is related to human papillomavirus (HPV) infection, viral persistence, progression, and invasion. Therefore, the immune response is linked to HPV status. Natural killer (NK) cells play a central role against virus-infected cells and tumours through a delicate balance between activating and inhibitory receptors and secretion of cytokines and chemokines. These cells also play a crucial role in tumour immunosurveillance. For these reasons, there is growing interest in harnessing NK cells as an immunotherapy for cervical cancer. These studies are diverse and include many strategies such as transferring activated autologous or allogeneic NK cells, improving the activation and cytolytic activity of NK cells using cytokines or analogues and modifying chimeric antigen receptors to increase specificity and targeting NK cells. However, research regarding the application of NK cells in immunotherapy is limited. This article focuses on recent discoveries about using NK cells to prevent and treat cervical cancer and the possibility of cellular immunotherapy becoming one of the best strategies to exploit the immune system to fight tumours.

Application of natural killer cells in pancreatic cancer.

Pancreatic cancer, a highly malignant disease, is characterized by rapid progression and early metastasis. Although the integrative treatment of pancreatic cancer has made great progress, the prognosis of patients with advanced pancreatic cancer remains extremely poor. In recent years, with the advancements in tumor immunology, immunotherapy has become a promising remedy for pancreatic cancer. Natural killer (NK) cells are the key lymphocytes in the innate immune system. NK cell function does not require antigen pre-sensitization and is not major histocompatibility complex restricted. By targeting tumors or virus-infected cells, the cells play a key role in immune surveillance. Although several questions about NK cells in pancreatic cancer still need to be further studied, there are extensive theories supporting the clinical application prospects of NK cell immunotherapy in pancreatic cancer. Since very few studies have evaluated the role of NK cells in pancreatic cancer, this review provides a comprehensive update of the role of NK cells in pancreatic cancer immunotherapy.

Accelerated extrinsic epigenetic aging and increased natural killer cells in blood of suicide completers

BackgroundStudies suggest aberrant DNA methylation in victims of suicide. Recently, DNA methylation profiles have been developed for determining “epigenetic age,” which is the most accurate estimate of biological age. Subsequently, two refined measures of epigenetic age acceleration have been expanded for blood samples as intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively). IEAA involves pure epigenetic aging independent of blood cell composition, whereas EEAA involves immunosenescence in association with blood cell composition. MethodsWe investigated epigenetic age acceleration using two independent DNA methylation datasets: a brain dataset from 16 suicide completers and 15 non-psychiatric controls and a blood dataset compiled using economical DNA pooling technique from 56 suicide completers and 60 living healthy controls. In the blood dataset, we considered IEAA and EEAA, as well as DNA methylation-based blood cell composition. ResultsThere was no significant difference in universal epigenetic age acceleration between suicide completers and controls in both brain and blood datasets. Blood of suicide completers exhibited an increase in EEAA, but not in IEAA. We additionally found that suicide completers had more natural killer cells but fewer granulocytes compared to controls. ConclusionThis study provides novel evidence for accelerated extrinsic epigenetic aging in suicide completers and for the potential application of natural killer cells as a biomarker for suicidal behavior.

Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells.

Relapsed acute myeloid leukemia (AML) is a significant post-transplant complication lacking standard treatment and associated with a poor prognosis. Cellular therapy, which is already widely used as a treatment for several hematological malignancies, could be a potential treatment alternative. Natural killer (NK) cells play an important role in relapse control but can be inhibited by the leukemia cells highly positive for HLA class I. In order to restore NK cell activity after their ex vivo activation, NK cells can be combined with conditioning target cells. In this study, we tested NK cell activity against KG1a (AML cell line) with and without two types of pretreatment—Ara-C treatment that induced NKG2D ligands (increased activating signal) and/or blocking of HLA–KIR (killer-immunoglobulin-like receptors) interaction (decreased inhibitory signal). Both treatments improved NK cell killing activity. Compared with target cell killing of NK cells alone (38%), co-culture with Ara-C treated KG1a target cells increased the killing to 80%. Anti-HLA blocking antibody treatment increased the proportion of dead KG1a cells to 53%. Interestingly, the use of the combination treatment improved the killing potential to led to the death of 85% of KG1a cells. The combination of Ara-C and ex vivo activation of NK cells has the potential to be a feasible approach to treat relapsed AML after hematopoietic stem cell transplantation.

Application of NK Cells in ASCT Peritransplantation of Multiple Myeloma

BACKGROUNDSignificant progress has been made in the therapy of multiple myeloma (MM) with the autologous hematopoietic stem cell transplantation(ASCT) in recent years. But the relapse after transplantation is still the main problem because the grafts are often contaminated by tumor cells and have no effect of anti myeloma. The residual myeloma cells are reduced by increasing doses of cytotoxic drug in the pretreatment. But the related mortality of ASCT is increased because of side effects and complications. Therefore, the pretreatment of MM hasn't changed very much in recent 50 years. So it is urgent to find a new pretreatment to improve curative effect which has small side effects. Natural killer (NK) cells are the principal effector cells in the innate immune system. They have extensive biological functions including anti-tumor and antiviral effects, etc. There is no report about applying NK cells as a pretreatment for ASCT to treat MM so far. In this study, NK cells were added to the pretreatment of ASCT to treat MM We hope NK cells can increase the curative effect and reduce relapse rate, but not increase the side effects. Meanwhile, they can clear myeloma cells without killing by chemotherapy drugs and to decrease infection in transplantation.OBJECTIVETo observe the safety and effectiveness of the technology by applying NK cells in peritransplantation of MM ASCT.METHODSThe ages of 8 MM patients including 7 males and 1 female were 42-62 years, the median age was 51 years, 2 patents of CR and 6 patents of PR before transplantation. The method of NK cell culture: membrane embedded active factor culture system. The pretreatment mainly based on standard Melphalan or busulfan. NK cells were infused to 2 cases back 6-7days after infusing stem cell, and to 6 cases back 24-48 hours before infusing stem cells and 48 hours after chemotherapy as a part of pretreatment in transplantation. Stem cell infusion volume: the number of CD34+ cell 2.2-4.0×106/kg, the number of mononuclear cells 4.3-5.8×106/kg. NK cell infusion volume: 16-160×106/kg. we observed the adverse reactions, recovery time of blood cells and the curative effects.RESULTSThere were no instances of fever, rash, diarrhea,shock, and other adverse reactions in this study. Recovery time of hematopoietic cells was: 7-14d of granulocyte and 9d of the median time, 9-34d of platelet and 11d of the median time. Fever(38-39 degrees) occurred in 6 patients during the inhibitory period of bone marrow after ASCT. Infection is the major cause of fever in patients receiving ASCT. We evaluated therapeutic effect 3 months after transplantation was 3 cases of CR and 5 cases of PR in 8 patients. The effect 6 months after transplantation was 3 cases of CR and 3 cases of PR in 6 patients. 8 patients were given thalidomide for maintenance therapy. The follow-up time was 3-29 months, median follow-up time was 11 months. Up to the present, there was no death case.CONCLUSIONSIt was safe and effective to infuse autologous NK cells back in peritransplantation of MM ASCT. Storm effect of inflammatory factors didn't occur during this study. We will expand the number of cases for further clinical research to observe the long-term therapeutic effects and adverse reactions. DisclosuresNo relevant conflicts of interest to declare.

P67. Targeted natural killer (NK) cell based adoptive immunotherapy for the treatment of patients with non-small cell lung cancer (NSCLC) after radiochemotherapy (RCT) – clinical application of NK cells activated by heat shock protein 70 (Hsp70)

Meeting abstracts Membrane-bound Hsp70 serves as a recognition structure for NK cells that were pre-stimulated with Hsp70 peptide TKD plus low dose IL-2 in vitro and in mouse models. In a clinical phase I trial feasibility, safety and tolerability of ex vivo TKD/IL-2 stimulated autologous NK cells

Advantages and clinical applications of natural killer cells in cancer immunotherapy

The past decade has witnessed a burgeoning of research and further insight into the biology and clinical applications of natural killer (NK) cells. Once thought to be simple innate cells important only as cytotoxic effector cells, our understanding of NK cells has grown to include memory-like responses, the guidance of adaptive responses, tissue repair, and a delicate paradigm for how NK cells become activated now termed "licensing" or "arming." Although these cells were initially discovered and named for their spontaneous ability to kill tumor cells, manipulating NK cells in therapeutic settings has proved difficult and complex in part due to our emerging understanding of their biology. Therapies involving NK cells may either activate endogenous NK cells or involve transfers of exogenous cells by hematopoietic stem cell transplantation or adoptive cell therapy. Here, we review the basic biology of NK cells, highlighting characteristics which make NK cells particularly useful in cancer therapies. We also explore current treatment strategies that have been used for cancer as well as discuss potential future directions for the field.