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Adoptive cell therapy (ACT) is a promising treatment that is considered safe and efficient. Natural killer (NK) cells play an important role in the innate immune system and destroy target cells such as tumor cells without prior sensitization. Here, we report a 59-year-old man with advanced diffuse hepatocellular carcinoma (HCC) who underwent 17 courses of NK cell treatment from March 2017 to July 2018. Although he presented with progressive disease, his hydrothorax and ascites decreased, and his state of mind, appetite and quality of life were markedly improved after treatment versus at admission. To date, his survival time is >48 months. Here, we provide evidence that NK cell adoptive therapy has no adverse effects, enhances immune function, and improves the quality of life of patients with HCC.
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Background: Natural killer (NK) cells can be used as an adoptive immunotherapy to treat cancer patients. Purpose: In this study, we evaluated the efficacy of highly activated NK (HANK) cell immunotherapy in patients with advanced lung cancer. Patients and methods: Between March 2016 and September 2017, we enrolled 13 patients who met the enrollment criteria. Donor peripheral blood monocytes were isolated from patients and the NK cells were expanded. After 12 days of culture, the cells were collected and infused intravenously on days 13 to 15. The enrolled patients received at least one course including three times of infusions. The lymphocyte subsets, cytokine production, and the expression of carcinoembryonic antigen (CEA) and thymidine kinase 1 (TK1) were measured before treatment and after the last infusion. Results: No side effects were observed. After a three-month follow-up, the percentage of patients who achieved stable disease and progressive disease was 84.6% and 15.4%. Moreover, the level of IFN-γ was significantly higher after treatment and the level of CEA decreased substantially. The overall immune function of the patients who received the NK cell therapy remained stable. Conclusion: This is the first study to describe the efficacy of NK cell therapy of patients with advanced lung cancer. These clinical observations demonstrated that NK cell is safe and efficient for advanced lung cancer therapy.
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For advanced hepatocellular carcinoma (HCC) patients, liver transplantation (LT) is an optimal treatment with limitation of high risk of tumor recurrence related to the immunosuppressive chemotherapy as usually recommended. In this study, a 29-year-old man suffered from HCC recurrence after LT. He underwent radiotherapy (total dose: 45 Gy) but had no significant response. Then, he received iodine-125 seed implantation combined with allogenic natural killer (NK) cell immunotherapy. Liver function, immune function, circulating tumor cell counts and computed tomography scans were evaluated to determine the clinical effect. We found that this combined treatment produced enhanced immune function of the patient and reduction in tumor size. This is the first report of an efficacy and safety study about clinical regimen comprising allogenic NK cell immunotherapy combined with iodine-125 seed implantation for the treatment of HCC recurrence after LT.
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[This corrects the article DOI: 10.3892/mco.2017.1230.].
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Masses are often detected in the abdomen of patients with sizeable ovarian cancer. There are currently no effective treatments available for late-stage ovarian cancer. Immunotherapy is gaining increasing attention worldwide in the clinical setting due to its ability to eliminate tumor cells and its favorable toxicity profile. We herein report the case of a 60-year-old woman who received allogenic natural killer (NK) cell immunotherapy for a sizeable ovarian carcinoma and achieved a noteworthy response. NK cells were isolated from the donor's peripheral blood mononuclear cells, and the cell numbers were increased to 8-10 billion [corrected]. The activated cells were expanded ex vivo for 14 days prior to intravenous infusion. After six infusions of NK cell therapy >3 months, the level of carbohydrate antigen 125 decreased significantly (from 11,270 to 580 U/ml). Furthermore, the size of the masses in the abdomen was markedly reduced. Overall, the treatment had few adverse effects and it prolonged patient survival. The present data and the patient response suggest that allogenic NK cell immunotherapy is a promising approach for ovarian cancer, with few treatment-related adverse effects. The patient received six intravenous infusions of allogenic HANK cells between March, 2015 and June, 2015, but discontinued in October, 2015 and succumbed to the disease in March, 2016 following relapse.
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We investigated the effectiveness of adoptive transfer of KIR ligand-mismatched highly activated nature killer (HANK) cells in patients with hepatic carcinoma. Peripheral blood mononuclear cells were obtained and cultured in vitro to induce expansion and activation of HANK cells. After 12 d of culture, the cells were divided into 3 parts and infused intravenously on days 13 to 15. The patients (n = 16) were given one to 6 courses of immunotherapy. No side effects were observed. The lymphocyte subsets and cytokine, thymidine kinase 1 (TK1) and circulating tumor cell (CTC) levels were measured 1 day before treatment and 1 month after the final infusion: the absolute number of total T cells and NK cells and the IL-2 and TNF-ß levels were significantly higher, and the TK1 and CTC levels were significantly lower at 1 month after treatment. The percentage of patients who experienced partial response, disease stabilization, and disease progression at 3 months after treatment was 18.8%, 50.0% and 31.2%, respectively. The total follow-up period was 2-12 months. The median progression-free survival from treatment was 7.5 months. This is the first study on the benefits of HANK cell immunotherapy for hepatic carcinoma These encouraging preliminary observations imply that HANK cell immunotherapy is safe, can improve the immune function of patients with liver cancer, and may even reduce the rate of tumor metastasis and recurrence. However, further studies on larger samples of patients with a longer follow-up period are required to confirm these findings.
