natural killer (nk) cells are an essential part of tumor immunosurveillance, evidenced by higher cancer susceptibility and metastasis in association with diminished nk activity in mouse models and clinical studies [1,2,3]. the natural cytotoxic receptor nkp46 is also often used to identify mouse and human nk cells in combination with the absence of cd3 expression. nk cells are mounted with a repertoire of inhibitory and activating surface receptors (table 1) [25,26,27,28,29]. miller et al. a wide range of tumor antigens have been targeted by car-nk cells in pre-clinical studies for hematological malignancies and solid tumors [38, 39, 41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76]. vallera et al. lee et al. wang et al. a novel source of nk cells has emerged to circumvent many of the challenges associated with nk cell therapy. the anti-tumor response of lak cells was shown attributed mainly to nk cells . the expansion of nk cells using il-2 alone is relatively modest and typically results in only several cell divisions in medium containing 1000 u/ml of il-2 . masuyama et al. clinical evaluation of safety and efficacy of nk cells under this expansion is warranted. the difficulty to obtain large quantity of nk cells, to expand to clinical scale ex vivo, and to sustain in vivo survival and activity of infused nk cells has encumbered the progress. successful adoptive transfer and in vivo expansion of human haploidentical nk cells in patients with cancer. gao y, et al. hammer q, et al. nkp44-nkp44 ligand interactions in the regulation of natural killer cells and other innate lymphoid cells in humans. natural killer (nk) cells inhibit systemic metastasis of glioblastoma cells and have therapeutic effects against glioblastomas in the brain. li y, et al.
et al. a combinational therapy of egfr-car nk cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases. dnam1 and 2b4 costimulatory domains enhance the cytotoxicity of anti-gpc3 chimeric antigen receptor-modified natural killer cells against hepatocellular cancer cells in vitro. expression of il-15 in nk cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor. esser r, et al. retargeting of natural killer-cell cytolytic activity to erbb2-expressing cancer cells results in efficient and selective tumor cell destruction. han j, et al. synergy among receptors on resting nk cells for the activation of natural cytotoxicity and cytokine secretion. tumor-primed human natural killer cells lyse nk-resistant tumor targets: evidence of a two-stage process in resting nk cell activation. lee j, et al. ex vivo-expanded nk cells from blood and ascites of ovarian cancer patients are cytotoxic against autologous primary ovarian cancer cells. characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy. zeng j, et al. choi i, et al. expansion of highly cytotoxic human natural killer cells for cancer cell therapy. membrane bound il-21 based nk cell feeder cells drive robust expansion and metabolic activation of nk cells. ex vivo expansion of highly cytotoxic human nk cells by cocultivation with irradiated tumor cells for adoptive immunotherapy. highly efficient il-21 and feeder cell-driven ex vivo expansion of human nk cells with therapeutic activity in a xenograft mouse model of melanoma. ex vivo activation and expansion of natural killer cells from patients with advanced cancer with feeder cells from healthy volunteers. masuyama j, et al. markers and function of human nk cells in normal and pathological conditions.
in general, the development of nk cell-directed therapies has two main focal points: optimizing the source of therapeutic nk cells for adoptive transfer and enhancing nk cell cytotoxicity and persistence in vivo. j. immunol. wagner, j. a. et al. romee, r. et al. schlums, h. et al. molgora, m. et al. viel, s. et al. parodi, m. et al. wu, j. d. et al. molgora, m. et al. veluchamy, j. p. et al. miller, j. s. et al. luevano, m. et al. spanholtz, j. et al. knorr, d. a. et al. schuster, s. j. et al. neelapu, s. s. et al. denman, c. j. et al. cichocki, f. et al.
romee, r. et al. rosenberg, s. a. et al. burns, l. j. et al. rosenberg, s. a. et al. bergamaschi, c. et al. klebanoff, c. a. et al. miller, j. s. et al. wrangle, j. m. et al. sarhan, d. et al. carlsten, m. et al. vey, n. et al. blake, s. j. et al. pesce, s. et al. hsu, j. et al. xu, l. et al. triebel, f. et al. blackburn, s. d. et al. taborda, n. a. et al. exploring the nk cell platform for cancer immunotherapy.
due to their innate ability to eliminate tumor cells, nk cell-based immunotherapies against cancer have been investigated for decades. early nearly 20 years ago, nk cell-mediated immunotherapy emerged as a safe and effective treatment approach for patients with advanced-stage given their potent antitumour activity, therapeutic manipulation of nk cells provides an attractive strategy for cancer treatment., nk cells cancer immunotherapy, nk cells cancer immunotherapy, car-nk cells: a promising cellular immunotherapy for cancer, nk cell therapy for cancer, nk cell therapy in solid tumors.
several clinical studies have reported nk cell-based immunotherapy to be a promising treatment for cancer. in patients with cancer, nk cell function is 1) nk cells are the first responders of the immune system and can directly recognize and lyse tumor cells. activating receptors on nk cells cancer immunotherapy has been firmly established as a new milestone for cancer therapy, with the development of multiple immune cells as, exploring the nk cell platform for cancer immunotherapy, nk cell therapy cost, nk cell therapy fda approval, nk cell therapy side effects, how do nk cells kill cancer cells, nk cell therapy review, nk cell activation, nk cell therapy clinical trials, allogeneic nk cell therapy, nk cell persistence.
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