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.
persistence and in vivo expansion of nk cells depends on lymphodepleting chemotherapy to make space and induce release of endogenous il-15. the potential role of allogeneic nk cells in cancer elimination has been more difficult to demonstrate. several lines of evidence suggest that functional activity of mature nk cells can be reset when the cells are exposed to changed mhcs and that nk-cell education is a continuous process. these findings are important to nk-cell immunotherapy; they suggest that donor nk cells unlicensed by hla alleles absent in the donor may become licensed by host hla alleles, leading to activity of donor nk cells against host tumor cells lacking hla expression.31 in clinical trials using allogeneic t-cell–depleted hematopoietic cell transplantation from haploidentical donors in patients with aml, rugierri et al.
however, it is important to recognize that the absolute level of in vivo nk cell expansion needed to induce a clinical response remains unknown. importantly, we observed that the process of cd56 selection resulted in threefold fewer nk cells per product compared with cd3 depletion alone. nevertheless, one patient experienced prolonged nk-cell persistence despite interruption of il-2 therapy and corticosteroid use, suggesting that the expansion of allogeneic nk cells in patients with solid tumor is possible. the studies discussed here provide clinical evidence of a solid basis for development of future strategies to manipulate nk-cell product, host, and target. future clinical trials will be designed to exploit strategies to overcome the host immune barriers of nk anti-tumor reactivity.
due to their innate ability to eliminate tumor cells, nk cell-based immunotherapies against cancer have been investigated for decades. early a cancer treatment approach known as immunotherapy has become popular in the medical field. in this case, immune cells are boosted for effective natural killer (nk) cells recognize targets stressed by malignant transformation or infection and can be long-lived. they become educated by interacting, nk cell therapy in solid tumors, nk cell therapy fda approval, nk cell therapy fda approval, natural killer cells treatment, nk cell therapy cost.
natural killer cell therapy is a type of cellular immunotherapy, just like car t-cell therapy. like t-cells, nk cells form part of the immune system and attack germs and other malignant cells. unlike t-cells, however, nk cells are not tailored to specific antigens. cell therapy, a new approach that uses immune cells to attack tumors, has emerged as one of the most promising breakthroughs in cancer treatment. first in the last years, natural killer (nk) cell-based immunotherapy has emerged as a promising therapeutic approach for solid tumors and cell therapy is an innovative therapeutic concept where viable cells are implanted, infused, or grafted into a, nk cell therapy clinical trials, nk cell therapy companies.
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