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1

Qiao, Wenhua, Peng Dong, Hui Chen, and Jianmin Zhang. "Advances in Induced Pluripotent Stem Cell-Derived Natural Killer Cell Therapy." Cells 13, no. 23 (2024): 1976. http://dx.doi.org/10.3390/cells13231976.

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Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system capable of killing virus-infected cells and/or cancer cells. The commonly used NK cells for therapeutic applications include primary NK cells and immortalized NK cell lines. However, primary NK cell therapy faces limitations due to its restricted proliferation capacity and challenges in stable storage. Meanwhile, the immortalized NK-92 cell line requires irradiation prior to infusion, which reduces its cytotoxic activity, providing a ready-made alternative and overcoming these bottlenecks. Recent improvements in di
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Wang, Hua, Bi-bo Fu, Robert Peter Gale, and Yang Liang. "NK-/T-cell lymphomas." Leukemia 35, no. 9 (2021): 2460–68. http://dx.doi.org/10.1038/s41375-021-01313-2.

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AbstractNatural killer/T-cell lymphoma (NKTL) is a sub-type of Epstein–Barr virus (EBV)-related non-Hodgkin lymphomas common in Asia and Latin America but rare elsewhere. Its pathogenesis is complex and incompletely understood. Lymphoma cells are transformed from NK- or T-cells, sometimes both. EBV-infection and subsequent genetic alterations in infected cells are central to NKTL development. Hemophagocytic syndrome is a common complication. Accurate staging is important to predict outcomes but there is controversy which system is best. More than two-thirds of NKTL lympohmas are localized at d
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Lachota, Mieszko, Marianna Vincenti, Magdalena Winiarska, Kjetil Boye, Radosław Zagożdżon, and Karl-Johan Malmberg. "Prospects for NK Cell Therapy of Sarcoma." Cancers 12, no. 12 (2020): 3719. http://dx.doi.org/10.3390/cancers12123719.

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Natural killer (NK) cells are innate lymphoid cells with potent antitumor activity. One of the most NK cell cytotoxicity-sensitive tumor types is sarcoma, an aggressive mesenchyme-derived neoplasm. While a combination of radical surgery and radio- and chemotherapy can successfully control local disease, patients with advanced sarcomas remain refractory to current treatment regimens, calling for novel therapeutic strategies. There is accumulating evidence for NK cell-mediated immunosurveillance of sarcoma cells during all stages of the disease, highlighting the potential of using NK cells as a
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Hurton, Lenka, R. Iram Siddik, Harjeet Singh, et al. "Identifying NK-Cell Donors for Cell Therapy Based on Functional Phenotype." Blood 110, no. 11 (2007): 3271. http://dx.doi.org/10.1182/blood.v110.11.3271.3271.

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Abstract Donor natural killer (NK) cells after haploidentical hematopoietic stem-cell transplantation (HSCT) and infusion of haploidentical NK-cells have demonstrated a therapeutic effect. NK alloreactivity resulting from appropriate Killer cell Ig-like receptor (KIR)-ligand disparity in human-leukocyte-antigen (HLA)-haplotype mismatched HSCT has resulted in improved engraftment and decreased incidence of leukemia relapse. Yet, not all patient-donor pairs benefit for an allogeneic NK-cell effect. To identify NK-cell donors with a suitable KIR-ligand mismatch, we have developed a functional ass
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Parameswaran, Reshmi, David N. Wald, Marcos De Lima, Dean A. Lee, and Stephen Moreton. "Novel Approach for NK Cell Therapy for Cancer." Blood 124, no. 21 (2014): 3836. http://dx.doi.org/10.1182/blood.v124.21.3836.3836.

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Abstract Novel therapeutic approaches are urgently needed for many malignancies such as Acute Myeloid Leukemia (AML). We have developed a new therapeutic strategy based upon NK cell immunotherapy that exhibits high clinical potential based upon cell and animal studies. While the harnessing of NK cells for cellular therapy against malignancies has been a topic of interest for several decades, our approach overcomes a major hurdle of insufficient NK cell cytotoxic activity. We have identified that targeting the kinase GSK3 through pharmacologic and genetic approaches leads to the hyperactivation
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Chu, Yaya, Margaret Lamb, Mitchell S. Cairo, and Dean A. Lee. "The Future of Natural Killer Cell Immunotherapy for B Cell Non-Hodgkin Lymphoma (B Cell NHL)." Current Treatment Options in Oncology 23, no. 3 (2022): 381–403. http://dx.doi.org/10.1007/s11864-021-00932-2.

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Opinion statementNatural killer (NK) cells have played a critical—if largely unrecognized or ignored—role in the treatment of B cell non-Hodgkin lymphoma (NHL) since the introduction of CD20-directed immunotherapy with rituximab as a cornerstone of therapy over 25 years ago. Engagement with NK cells leading to lysis of NHL targets through antibody-dependent cellular cytotoxicity (ADCC) is a critical component of rituximab’s mechanism of action. Despite this important role, the only aspect of B cell NHL therapy that has been adopted as standard therapy that even indirectly augments or restores
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Lyu, Jiaying. "Car-NK cell therapy for overcoming solid tumors." Highlights in Science, Engineering and Technology 36 (March 21, 2023): 1078–82. http://dx.doi.org/10.54097/hset.v36i.6177.

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There are many standard treatments for solid tumors, including surgery, chemotherapy, radiotherapy, or combination therapy, but all of them are difficult to maintain long-term anti-cancer effects. Recent immunotherapies such as Car-T have achieved remarkable results in hematologic cancers. However, clinical success of immunotherapy for solid tumors remains difficult to achieve due to the specific nature of solid tumor microenvironment and impediments to drug delivery. NK cell therapies can be divided into two main types, those that directly use unmodified NK cells to kill cancer cells and CAR-
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Valamehr, Bahram. "Advancing iPSC-derived NK cell therapy." Cell and Gene Therapy Insights 5, no. 12 (2019): 1655–61. http://dx.doi.org/10.18609/cgti.2019.173.

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Mehta, Rohtesh S., Brion Randolph, May Daher, and Katayoun Rezvani. "NK cell therapy for hematologic malignancies." International Journal of Hematology 107, no. 3 (2018): 262–70. http://dx.doi.org/10.1007/s12185-018-2407-5.

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Stoltzman, Carrie, Devikha Chandrasekaran, Erika von Euw, Cyd McKay, Christina Root, and Colleen Delaney. "Abstract 2 Development of CAR-NK Cell Therapy for Hematologic Malignancies." Stem Cells Translational Medicine 11, Supplement_1 (2022): S4. http://dx.doi.org/10.1093/stcltm/szac057.002.

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Abstract Introduction Natural killer (NK) cells can kill tumor cells without priming or prior activation through their complement of activating and inhibitory surface molecules. Chimeric antigen receptor (CAR) expression by engineered NK cells can improve both specificity and potency of the NK cells’ anti-tumor efficacy. CAR-NK cell therapy may be a safer, more clinically accessible, and cost effective allogeneic cellular therapy in comparison to autologous CAR-T cell therapy, as NK cells do not cause graft versus host disease (GvHD) or cytokine release syndrome (CRS). Objective We aimed to de
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Oh, Sooyeon, Joo-Ho Lee, KyuBum Kwack, and Sang-Woon Choi. "Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors." Cancers 11, no. 10 (2019): 1534. http://dx.doi.org/10.3390/cancers11101534.

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In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. Recent findings highlighted that NK cells can even target cancer stem cells. The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. In allogeneic
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Fedorova, P. O. "CAR natural killer cell therapy: Natural killer cell activation and expansion." Acta Biomedica Scientifica 9, no. 5 (2024): 53–65. http://dx.doi.org/10.29413/abs.2024-9.5.6.

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Currently, chimeric antigen receptor (CAR) T-cell therapy is an effective treatment method of hematological malignancies. However, T-lymphocyte-based immunotherapy has certain limitations for the scope of application of this approach. A promising alternative is CAR therapy based on natural killer (NK) cells, since it does not require detailed donor selection according to the human leukocyte antigen system; NK cells have a unique mechanism for recognizing and destroying tumor cells. In addition, NK cells do not cause severe toxic reactions when infused. The creation of a CAR NK product is a com
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Alvarez, Maite, та William Murphy. "Combination of IL-2 and anti-TGF-β increases natural killer cell reconstitution after hematopoietic stem cell transplantation (169.7)". Journal of Immunology 186, № 1_Supplement (2011): 169.7. http://dx.doi.org/10.4049/jimmunol.186.supp.169.7.

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Abstract Despite the efficacy of hematopoietic stem cell transplantation (HSCT) as a cancer therapy, cancer relapse remains a significant complication. Natural killer (NK) cells are the first lymphoid population to recover after HSCT and can kill transformed or virally-infected cells without prior sensitization. Therefore, accelerating NK cell reconstitution may improve HSCT therapy. We utilized the combination of administering the stimulatory cytokine, IL-2 concurrently with the blockade of the immunosuppressive cytokine, transforming growth factor-beta (TGF-β) as a possible therapy to accele
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Xiao, Jiani, Tianxiang Zhang, Fei Gao, et al. "Natural Killer Cells: A Promising Kit in the Adoptive Cell Therapy Toolbox." Cancers 14, no. 22 (2022): 5657. http://dx.doi.org/10.3390/cancers14225657.

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As an important component of the innate immune system, natural killer (NK) cells have gained increasing attention in adoptive cell therapy for their safety and efficacious tumor-killing effect. Unlike T cells which rely on the interaction between TCRs and specific peptide-MHC complexes, NK cells are more prone to be served as “off-the-shelf” cell therapy products due to their rapid recognition and killing of tumor cells without MHC restriction. In recent years, constantly emerging sources of therapeutic NK cells have provided flexible options for cancer immunotherapy. Advanced genetic engineer
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Lopez, Rebecca, Andreas Lundqvist, Stephanie Sellers, et al. "A Rhesus Macaque Model to Optimize Adoptive NK Cell Therapy." Blood 112, no. 11 (2008): 3905. http://dx.doi.org/10.1182/blood.v112.11.3905.3905.

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Abstract NK cell based immunotherapy represents a promising treatment approach for patients with cancer. Although preliminary clinical trials in humans suggest NK cell infusions can mediate anti-tumor effects, animal models are needed to provide insight into methods to enhance both the function and in vivo longevity of adoptively infused NK cells. Research conducted in our laboratory has shown that ex vivo expanded human NK cells are highly activated, up-regulating NKG2D, Granzyme B, TRAIL and Fas-ligand expression making them much more cytotoxic to tumor cells compared to freshly isolated NK
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Sordo-Bahamonde, Christian, Massimo Vitale, Seila Lorenzo-Herrero, Alejandro López-Soto, and Segundo Gonzalez. "Mechanisms of Resistance to NK Cell Immunotherapy." Cancers 12, no. 4 (2020): 893. http://dx.doi.org/10.3390/cancers12040893.

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Immunotherapy has recently been a major breakthrough in cancer treatment. Natural killer (NK) cells are suitable targets for immunotherapy owing to their potent cytotoxic activity that may target cancer cells in a major histocompatibility complex (MHC) and antigen-unrestricted manner. Current therapies targeting NK cells include monoclonal antibodies that promote NK cell antibody-dependent cell-mediated cytotoxicity (ADCC), hematopoietic stem cell transplantation (HSCT), the adoptive transfer of NK cells, the redirection of NK cells using chimeric antigen receptor (CAR)-NK cells and the use of
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Li, Junyi, and Yanzhang Wei. "Combination cancer therapy integrating T-cell immune checkpoint blockers and natural killer cell activation." Gene & Protein in Disease 3, no. 4 (2024): 3804. https://doi.org/10.36922/gpd.3804.

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T-cell immune checkpoint blockers (ICBs) and natural killer (NK) cell activation have emerged as promising strategies for cancer therapy in recent years. In this approach, ICBs target inhibitory receptors on cytotoxic immune cells, such as programmed death Protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), to enhance immune cell cytotoxicity against cancer cells in a CD8+ T cell-dependent manner. Meanwhile, NK cells play a critical role in immunosurveillance through their direct cytotoxic effects, which do not require prior activation. NK cell activation is mediated by receptors such as
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Bi, Jiacheng, Chen Huang, Xiaomeng Jin, et al. "TIPE2deletion improves the therapeutic potential of adoptively transferred NK cells." Journal for ImmunoTherapy of Cancer 11, no. 2 (2023): e006002. http://dx.doi.org/10.1136/jitc-2022-006002.

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BackgroundTo enhance the efficacy of adoptive NK cell therapy against solid tumors, NK cells must be modified to resist exhaustion in the tumor microenvironment (TME). However, the molecular checkpoint underlying NK cell exhaustion in the TME remains elusive.MethodsWe analyzed the correlation betweenTIPE2expression and NK cell functional exhaustion in the TME both in humans and mice by single-cell transcriptomic analysis and by using gene reporter mice. We investigated the effects ofTIPE2deletion on adoptively transferred NK cell therapy against cancers by using NK cells from NK-specificTipe2-
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Jiang, Yanyu. "Prospect Of CAR-NK Cell In Tumor Immunotherapy." Highlights in Science, Engineering and Technology 74 (December 29, 2023): 1042–48. http://dx.doi.org/10.54097/radssw50.

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The innate immune system has gained significant interest expected to the impressive natural killer (NK) cells ability to surveil and combat pathogens, regardless of major histocompatibility complex. Following the resounding success of CAR-T cell therapy, there has been a burgeoning interest in harnessing the NK therapeutics potential in recent years. Owing to its clinical triumphs, which those achieved by CAR-T cell therapy, this subject has garnered a discernible level of fascination. A captivating realm of investigation within tumor immunotherapy lies in delving into chimeric antigen recepto
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Kim, Dong Hwan, Suzanne Kamel-Reid, Hong Chang, et al. "Natural Killer (NK) or NK/T Cell Lineage Large Granular Lymphocytosis Associated with Dasatinib Therapy for Philadelphia Chromosome Positive Leukemia." Blood 112, no. 11 (2008): 933. http://dx.doi.org/10.1182/blood.v112.11.933.933.

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Abstract Dasatinib, a dual tyrosine kinase inhibitor, is known to modulate or suppress T-cell activation and proliferation. We report a series of patients of chronic peripheral lymphocytosis development, identified as natural killer (NK) cells or NK/T-cells based on their large granular lymphocyte (LGL) morphologies and CD16+CD56+CD3− or CD3+ immunophenotypic profiles during dasatinib therapy. All cases that developed LGL lymphocytosis achieved optimal molecular response (8/8 in LGL+ patients vs 3/10 in LGL− patients, p=0.002). A 51Cr release assay demonstrated that NK cell cytotoxicity has be
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Greer, John P. "Therapy of Peripheral T/NK Neoplasms." Hematology 2006, no. 1 (2006): 331–37. http://dx.doi.org/10.1182/asheducation-2006.1.331.

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AbstractThe mature T/natural killer (NK) lymphoma/leukemias represent 5–15% of all non-Hodgkin lymphoma. These diseases have a geographic variation, with more nodal disease in North America and Europe, including peripheral T cell lymphomas, unspecified, anaplastic large cell lymphoma, and angioimmunoblastic T cell lymphoma; and more extranodal disease in Asia due to Epstein-Barr virus–related nasal NK/T lymphoma and human T-cell leukemia virus (HTLV)-1–associated adult T cell leukemia/lymphoma. The prognosis in most peripheral T/NK neoplasms is poor, with 5-year survival less than 30%. Progres
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Du, Nawen, Feifei Guo, Yufeng Wang, and Jiuwei Cui. "NK Cell Therapy: A Rising Star in Cancer Treatment." Cancers 13, no. 16 (2021): 4129. http://dx.doi.org/10.3390/cancers13164129.

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Immunotherapy has become a robust and routine treatment strategy for patients with cancer; however, there are efficacy and safety issues that should be resolved. Natural killer (NK) cells are important innate immune cells that have attracted increasing attention owing to their major histocompatibility complex-independent immunosurveillance ability. These cells provide the first-line defense against carcinogenesis and are closely related to cancer development. However, NK cells are functionally suppressed owing to multiple immunosuppressive factors in the tumor microenvironment; thus, releasing
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Testa, Ugo, Germana Castelli, and Elvira Pelosi. "Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies." Cancers 17, no. 9 (2025): 1454. https://doi.org/10.3390/cancers17091454.

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The clinical use of T lymphocytes engineered with chimeric antigen receptors (CARs) has revolutionized the treatment of patients with refractory or relapsed hematological malignancies. CAR natural killer (CAR-NK) cells are NK cells engineered with CARs to specifically target cell antigens expressed on the membrane of tumor cells. CAR-NK cells could offer some advantages with respect to CAR-T cells, related to their specific and innate anti-tumor activity, availability as an “off the shelf” cellular therapy, reduced costs, and improved safety. Promising efficacy of CAR-Nk cell therapy was obser
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Maia, Andreia, Mubin Tarannum, Joana R. Lérias, et al. "Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy." Cells 13, no. 5 (2024): 451. http://dx.doi.org/10.3390/cells13050451.

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Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited in vivo persistence, reduced tumor infiltration, and low absolute NK cell numbers. This review outlines several strategies aiming to overcome these challenges. The developed strategies inclu
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Rethacker, Louise, Hugo Romero, Joshua Dulong, et al. "CRISPR Screens Identify Key Regulators of NK Cell Cytotoxicity in Cancer Therapy." Journal of Immunology 212, no. 1_Supplement (2024): 0445_5642. http://dx.doi.org/10.4049/jimmunol.212.supp.0445.5642.

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Abstract Natural Killer (NK) cells are innate lymphocytes that exhibit cytotoxic activity against cancer cells and are associated with a good prognosis when present in solid tumors. In the past, NK cells have been used in adoptive cell transfer to treat various cancers with modest relative success. More recently, NK cells modified with chimeric antigen receptor (CAR-NK cells) are being explored as a potential off-the-shelf therapy. However, mechanisms preventing the full cytotoxic anti-tumor activity of NK cells remain understudied. To unveil the key genes that govern the activation and inhibi
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Xue, Bin, Christopher Harrod, Long Le, Julia Schueler, and Kolin C. Hribar. "Abstract 1235: Complex in vitro tumor models screen NK therapy and reveal mode of action." Cancer Research 85, no. 8_Supplement_1 (2025): 1235. https://doi.org/10.1158/1538-7445.am2025-1235.

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Abstract NK cell therapy is an emerging and increasingly promising modality for various cancers. Whereas T cell-based adoptive cell therapy (e.g. tumor infiltrating lymphocytes or TILs, and CAR-T) is mainly limited to patient’s autologous cells due to concerns around allogeneic responses with MHC (major histocompatibility complex) mismatch, NK therapies do not suffer from this due to their low risk of introducing GvHD (Graft-versus-host disease), enabling the development of NK therapies using either patient-sourced NK cells or allogeneic, healthy donor-sourced cells. NK therapies have demonstr
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Barrow, Alexander, and Marco Colonna. "Exploiting NK Cell Surveillance Pathways for Cancer Therapy." Cancers 11, no. 1 (2019): 55. http://dx.doi.org/10.3390/cancers11010055.

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Natural killer (NK) cells can evoke potent anti-tumour activity. This function is largely mediated through a battery of specialised cell-surface receptors which probe the tissue microenvironment for changes in surface and secretory phenotypes that may alert to the presence of infection or malignancy. These receptors have the potential to arouse the robust cytotoxic and cytokine-secreting functions of NK cells and so must be tightly regulated to prevent autoimmunity. However, such functions also hold great promise for clinical intervention. In this review, we highlight some of the latest breakt
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Meiliana, Anna, Nurrani Mustika Dewi, and Andi Wijaya. "Prospect of Natural Killer Cells in Cancer Imunotherapy." Indonesian Biomedical Journal 10, no. 3 (2018): 192–202. http://dx.doi.org/10.18585/inabj.v10i3.532.

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BACKGROUND: Current understanding in molecular character of natural killer (NK) cell, its function and mechanisms, send people the ideas to develop a NK-cell-based immunotherapeutic strategies against human cancer.CONTENT: Before being regards as a cell-based cellular therapy, NK cell have to be clinical proven. Early studies with NK cells infusions for acute myeloid leukemia and lung cancer showed a promising result. NK cells need simplified methods for enriching and expanding, in addition to its transfection with chimeric antigen receptors (CARs). NK-92 arise as an assuring effector cells to
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Naranjo-Gomez, Mar, Marine Cahen, Jennifer Lambour, Myriam Boyer-Clavel, and Mireia Pelegrin. "Immunomodulatory Role of NK Cells during Antiviral Antibody Therapy." Vaccines 9, no. 2 (2021): 137. http://dx.doi.org/10.3390/vaccines9020137.

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Monoclonal antibodies (mAbs) are now considered as a therapeutic approach to prevent and treat severe viral infections. Using a mouse retroviral model, we showed that mAbs induce protective immunity (vaccinal effects). Here, we investigated the role of natural killer (NK) cells on this effect. NK cells are effector cells that are crucial to control viral propagation upon mAb treatment. However, their immunomodulatory activity during antiviral mAb immunotherapies has been little studied. Our data reveal that the mAb treatment of infected mice preserves the functional activation of NK cells. Imp
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Yang, Yuanzheng, Nancy Gordon, Eugenie S. Kleinerman, and Gangxiong Huang. "Promoting NK cell trafficking to improve therapeutic effect of NK cell therapy on osteosarcoma." Journal for ImmunoTherapy of Cancer 3, Suppl 2 (2015): P24. http://dx.doi.org/10.1186/2051-1426-3-s2-p24.

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Yang, Chaopin, Yue Li, Yaozhang Yang, and Zhiyi Chen. "Overview of Strategies to Improve Therapy against Tumors Using Natural Killer Cell." Journal of Immunology Research 2020 (January 21, 2020): 1–16. http://dx.doi.org/10.1155/2020/8459496.

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NK cells are lymphocytes with antitumor properties and can directly lyse tumor cells in a non-MHC-restricted manner. However, the tumor microenvironment affects the immune function of NK cells, which leads to immune evasion. This may be related to the pathogenesis of some diseases. Therefore, great efforts have been made to improve the immunotherapy effect of natural killer cells. NK cells from different sources can meet different clinical needs, in order to minimize the inhibition of NK cells and maximize the response potential of NK cells, for example, modification of NK cells can increase t
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Liu, Sizhe, Payal Dhar, and Jennifer D. Wu. "NK Cell Plasticity in Cancer." Journal of Clinical Medicine 8, no. 9 (2019): 1492. http://dx.doi.org/10.3390/jcm8091492.

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Natural killer (NK) cells are critical immune components in controlling tumor growth and dissemination. Given their innate capacity to eliminate tumor cells without prior sensitization, NK-based therapies for cancer are actively pursued pre-clinically and clinically. However, recent data suggest that tumors could induce functional alterations in NK cells, polarizing them to tumor-promoting phenotypes. The potential functional plasticity of NK cells in the context of tumors could lead to undesirable outcomes of NK-cell based therapies. In this review, we will summarize to-date evidence of tumor
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Shih, Alvin. "Realizing the potential of NK cell therapy." Immuno Oncology Insights 03, no. 01 (2022): 1–5. http://dx.doi.org/10.18609/ioi.2022.001.

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Miller, J. S. "NK cell therapy in cancer and transplantation." ISBT Science Series 7, no. 1 (2012): 157–59. http://dx.doi.org/10.1111/j.1751-2824.2012.01570.x.

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Suzuki, Ritsuro. "NK/T Cell Lymphoma: Updates in Therapy." Current Hematologic Malignancy Reports 13, no. 1 (2018): 7–12. http://dx.doi.org/10.1007/s11899-018-0430-5.

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Wolf, Natalie K., Chris Nicolai, Susanna Dang, et al. "Combination therapy to enhance NK cell anti-tumor responses." Journal of Immunology 204, no. 1_Supplement (2020): 88.10. http://dx.doi.org/10.4049/jimmunol.204.supp.88.10.

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Abstract Current cancer immunotherapies are targeted at mobilizing CD8 T cells, although numerous tumors have few or no antigens for CD8 T cells, or have lost MHC I, thereby evading CD8 T cells. There is therefore a need for improved therapies that mobilize other immune cells, such as NK cells, to the tumor microenvironment. A recent therapy candidate, cyclic dinucleotide (CDN), activates the cGAS-STING pathway of the innate immune system. Intratumoral CDN injections induce type I IFNs and other mediators that amplify the CD8 T cell response and induce regressions of primary tumors. MHC I-defi
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Verma, Divya, Mukesh Verma, and Rangnath Mishra. "Stem Cell Therapy and Innate Lymphoid Cells." Stem Cells International 2022 (August 2, 2022): 1–12. http://dx.doi.org/10.1155/2022/3530520.

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Innate lymphoid cells have the capability to communicate with other immune cell types to coordinate the immune system functioning during homeostasis and inflammation. However, these cells behave differently at the functional level, unlike T cells, these cells do not need antigen receptors for activation because they are activated by the interaction of their receptor ligation. In hematopoietic stem cell transplantation (HSCT), T cells and NK cells have been extensively studied but very few studies are available on ILCs. In this review, an attempt has been made to provide current information rel
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Liu, Xiao-ran, Bin Shao, Hui-ping Li, et al. "Combined peripheral natural killer (NK) cell and circulating tumor cell (CTC) enumeration to enhance prognostic efficiency in patients (pts) with triple-negative breast cancer (TNBC)." Journal of Clinical Oncology 35, no. 15_suppl (2017): 1105. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.1105.

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1105 Background: CTCs have emerged as an independent prognostic factor for metastatic breast cancer. However, the prognostic value of baseline CTCs regarding PFS in TNBC is still controversial, especially beyond first-line. We evaluated a novel combined NK cell/CTC detection system for enumeration to better understand the impact of cell count on prognosis in TNBC. Methods: 83 consecutive patients with metastatic TNBC were enrolled and received a new line of therapy (median=2, range: 1~5). Baseline circulating CTCs and NK cells were isolated and enumerated simultaneously prior to starting a new
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Wang, Xindi, Wenjing Luo, Lu Tang, Yu Hu, and Heng Mei. "Natural Killer-Cell Recovery in Patients Receiving CD19 CAR T-Cell Therapy: Dynamics and Clinical Significance." Blood 144, Supplement 1 (2024): 7217. https://doi.org/10.1182/blood-2024-205259.

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Background: Chimeric antigen receptor (CAR) T-cell therapy is an effective treatment for B-cell malignancies and systemic lupus erythematosus (SLE). However, due to the use of fludarabine and cyclophosphamide and the infusion of CAR T-cells, the immune-cell profile and immune reconstitution of patients will be affected. Current research on immune recovery mainly focuses on T cells, B cells, and neutrophils. The dynamics of natural killer (NK) cells, which are important anti-virus and anti-tumor cells, after CAR T-cell therapy remain unclear. Aim and Methods: The study aimed to track the dynami
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Molgora, Martina, Victor S. Cortez, and Marco Colonna. "Killing the Invaders: NK Cell Impact in Tumors and Anti-Tumor Therapy." Cancers 13, no. 4 (2021): 595. http://dx.doi.org/10.3390/cancers13040595.

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Natural Killer cells belong to group 1 innate lymphoid cells, which also includes ILC1s. NK/ILC1s are highly heterogeneous cell types showing distinct phenotypes across tissues and conditions. NK cells have long been described as innate lymphocytes able to directly and rapidly kill tumor cells without antigen-restriction. Different mechanisms were shown to modulate NK cell activation and tumor resistance, mainly based on cytokine stimulation and receptor–ligand interactions, and several strategies have been developed to target NK cells in tumor immunotherapy to promote NK cell function and ove
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Wang, Chao, Tingting Liu, Qin Wang, et al. "Abstract 6121: A novel allogeneic anti-DLL3 CAR-NK cell therapy in treating small cell lung cancer." Cancer Research 85, no. 8_Supplement_1 (2025): 6121. https://doi.org/10.1158/1538-7445.am2025-6121.

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Small cell lung cancer (SCLC) is an aggressively lethal malignancy with a high unmet medical need. Overexpression of Delta-like ligand 3 (DLL3) has been identified as a poor prognostic factor. Adoptive immunotherapy based on chimeric antigen receptor (CAR) T cells has been developed, however with significant adverse events. To address the critical need for an improved therapeutic intervention, we leveraged the ability of DLL3 targeted peripheral blood derived natural killer (PBNK) allogeneic cells therapy in treating SCLC. We describe preclinical in vitro and in vivo results demonstrating the
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Li, Lingyu, Jiuwei Cui, Chang Wang, et al. "Adoptive transfer of NK cells in combination with chemotherapy to improve outcomes of patients with locally advanced colon carcinoma." Journal of Clinical Oncology 35, no. 15_suppl (2017): e15038-e15038. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e15038.

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e15038 Background: The prognosis of advanced colon cancer (CC) patients remains disappointing, partly due to their greater proportion of CC-initiating cells (CICs), which is responsible for cancer drug-resistance and immune escape. Immunotherapies by harnessing the immune system to eliminate tumors have attracted broad attention. This study was to detect whether chemotherapy could enhance cytotoxicity of natural killer (NK) cells to CC cells (CCs), especially for CICs in vitro, and further evaluate the efficacy and safety of NK-cell therapy combined with chemotherapy in patients with local adv
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Fujisaki, Hiroyuki, Harumi Kakuda, Chihaya Imai, and Dario Campana. "Sustained Expansion of Human Natural Killer Cells for Leukemia Therapy." Blood 108, no. 11 (2006): 3719. http://dx.doi.org/10.1182/blood.v108.11.3719.3719.

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Natural killer (NK) cells are a promising tool for cell therapy of hematologic malignancies. They have potential for enhancing graft-versus-leukemia responses in recipients of hematopoietic stem cell transplant, and can also be used in a non-transplant setting, where haploidentical donor NK cells have been shown to expand in vivo. NK cells represent a small subset of peripheral blood cells. Hence, it can be problematic to obtain them in quantities sufficient to exert significant anti-leukemic activity in patients. We sought to identify culture conditions that would stimulate vigorous, sustaine
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Bareke, Halin, Adrián Ibáñez-Navarro, Pilar Guerra-García, et al. "Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas." International Journal of Molecular Sciences 24, no. 9 (2023): 8324. http://dx.doi.org/10.3390/ijms24098324.

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Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune
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Franks, S. Elizabeth, Benjamin Wolfson, and James W. Hodge. "Natural Born Killers: NK Cells in Cancer Therapy." Cancers 12, no. 8 (2020): 2131. http://dx.doi.org/10.3390/cancers12082131.

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Cellular therapy has emerged as an attractive option for the treatment of cancer, and adoptive transfer of chimeric antigen receptor (CAR) expressing T cells has gained FDA approval in hematologic malignancy. However, limited efficacy was observed using CAR-T therapy in solid tumors. Natural killer (NK) cells are crucial for tumor surveillance and exhibit potent killing capacity of aberrant cells in an antigen-independent manner. Adoptive transfer of unmodified allogeneic or autologous NK cells has shown limited clinical benefit due to factors including low cell number, low cytotoxicity and fa
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Aspirin, Angelica P., Aurelio A. de los Reyes V, and Yangjin Kim. "Polytherapeutic strategies with oncolytic virus–bortezomib and adjuvant NK cells in cancer treatment." Journal of The Royal Society Interface 18, no. 174 (2021): 20200669. http://dx.doi.org/10.1098/rsif.2020.0669.

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Proteasome inhibition and oncolytic virotherapy are two emerging targeted cancer therapies. Bortezomib, a proteasome inhibitor, disrupts the degradation of proteins in the cell leading to accumulation of unfolded proteins inducing apoptosis. On the other hand, oncolytic virotherapy uses genetically modified oncolytic viruses (OV) to infect cancer cells, induce cell lysis, and activate an antitumour response. In this work, optimal control theory is used to minimize the cancer cell population by identifying strategic infusion protocols of bortezomib, OV and natural killer (NK) cells. Three diffe
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Li, Wangshu, Xiuying Wang, Xu Zhang, Aziz ur Rehman Aziz, and Daqing Wang. "CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges." Biomolecules 14, no. 8 (2024): 1035. http://dx.doi.org/10.3390/biom14081035.

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The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains
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Klingemann, Hans-Georg, Carrie Grodman, Andreas K. Klein, et al. "Allogeneic NK Cell Therapy After Autologous Stem Cell Transplant: Results of a Phase I Study." Blood 116, no. 21 (2010): 4299. http://dx.doi.org/10.1182/blood.v116.21.4299.4299.

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Abstract Abstract 4299 Previous reports have shown that infusion of NK cells from a MHC mismatched donor can mediate an anti-leukemic effect in the recipient of an allogeneic hematopoietic stem cell transplant (HSCT). In this phase I study, we infused increasing numbers of allogeneic NK-cell enriched mononuclear cells (NK-MNC) from a MHC haplo-mismatched relative into patients who had recently undergone autologous stem cell transplant. We sought to determine whether infusion of mismatched, allogeneic NK-MNC cells was safe without concern for GvHD or graft rejection, and also whether cell colle
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Berrien-Elliott, Melissa M., Michelle Becker-Hapak, Amanda F. Cashen, et al. "Systemic IL-15 promotes allogeneic cell rejection in patients treated with natural killer cell adoptive therapy." Blood 139, no. 8 (2022): 1177–83. http://dx.doi.org/10.1182/blood.2021011532.

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Abstract Natural killer (NK) cells are a promising alternative to T cells for cancer immunotherapy. Adoptive therapies with allogeneic, cytokine-activated NK cells are being investigated in clinical trials. However, the optimal cytokine support after adoptive transfer to promote NK cell expansion, and persistence remains unclear. Correlative studies from 2 independent clinical trial cohorts treated with major histocompatibility complex-haploidentical NK cell therapy for relapsed/refractory acute myeloid leukemia revealed that cytokine support by systemic interleukin-15 (IL-15; N-803) resulted
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Yu, Xuan, Xiaobo Chen, Yanlong Yang, Yingsong Tian, Jie Jia, and Xinghe Tong. "Nanomaterial assisted natural killer cell therapy." Frontiers in Immunology 16 (May 5, 2025). https://doi.org/10.3389/fimmu.2025.1558701.

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The rising incidence of cancer has heightened interest in immune cell therapy, particularly the role of natural killer (NK) cells, which are essential components of the immune system. Their applications in tumor treatment have expanded significantly, especially with the incorporation of nanomaterials. This review comprehensively examines NK cell biology, encompassing aspects such as classification, distribution, receptor activation, and mechanisms of cytotoxicity. It also explores various NK cell therapies, including their sources, methods of acquisition, expansion techniques, Chimeric antigen
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