Rare types of cancer are often not effectively treated by approaches such as chemotherapy and radio-therapy, although their side-effects persist. Immunotherapy has been gaining attention worldwide with growing examples of its anticancer activity demonstrated in vivo. This case report describes a 35-year-old male who suffered from advanced epithelioid sarcoma and underwent 18 cycles of chemotherapy without any significant response, who suffered adverse effects that caused lung collapse. A notable response was observed following the administration of autologous immune enhancement therapy (AIET), which involves a process of isolation, activation and expansion of natural killer (NK) and T cells, which were obtained from the patient’s own (autologous) peripheral blood. With the present data and the response of the patient to AIET, it may be proposed that AIET is beneficial for patients suffering from advanced epithelioid sarcoma without producing adverse effects.
Current modalities of cancer treatment, including surgery, chemotherapy and radiotherapy, show marginal therapeutic responses in cancer patients. In adoptive immunotherapy, interleukin-2 (IL-2) activated immune cells demonstrated notable results in patients with advanced malignant disease. The present study reports the efficacy and safety of repetitive infusions of autologous immune enhancement therapy (AIET) in a stage IV colonic cancer patient who had already received first-line chemotherapeutic drugs. Peripheral blood was aspirated from the patient. Specifically, natural killer (NK) cells and T-lymphocytes were isolated from the peripheral blood mononuclear cells (PBMCs). These cells were activated and expanded ex vivo for 14 days and were transfused intravenously to the patient. After six infusions of AIET, the carcinoembryonic antigen (CEA) level was decreased from 901 to 437 U/ml, regression of lesions was noted and there were no adverse reactions during the course of this therapy. Thus, AIET may be a promising anticancer approach to eradicate tumor cells with other conventional therapies.
Immune cell-based therapies using natural killer (NK) cells and cytotoxic T cells are under constant scrutiny, with the aim to design an effective and reduced-toxicity therapy, which will benefit patients via improved quality of life and improved prognosis. Four patients with stage IV colon cancer were administered 1, 3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood was collected from the patients and the activation and expansion of NK and T cells was performed in Good Manufacturing Practice-certified clean rooms for ~12-15 days. Immunophenotypic analysis of the peripheral blood mononuclear cells (PBMCs) and expanded NK and T cells was conducted using flow cytometry and the patients were followed up. On average, 4.8×10 initial PBMCs and 2.7×10 total expanded cells were obtained. The intravenous infusions of the expanded cells were not accompanied by adverse reactions. Improved prognosis, reflected by a considerable decrease in the cancer markers, accompanied by an improved quality of life in the patients were observed. In conclusion, potential strategies are currently under development for the large-scale production of effectors cells; therefore, autologous immune enhancement therapy (AIET) may be considered as a viable approach to cancer treatment.
Although hydrogen peroxide (H2O2) is an admirable treatment for many cancer types, but the clinical impact of H2O2 on immune cells is not known. In the present study, we have demonstrated that H2O2 is a crucial factor to determine the cell mediated cytotoxicity of immune cells to the cancer cells. Natural killer (NK) cells and T cells were isolated from healthy donors and were activated and enriched the population at ex-vivo condition. At day14, activated NK and T cells were exposed to colon cancer cell at the ratio of 10:1 (Effector: Target) with or without H2O2 (50 µM and 100µM) treatment for 6 h and 12 h. Cytotoxicity assay showed that cytotolytic ability of NK and T cells was strongly suppressed in the presence of H2O2. H2O2 induced NK and T cell dysfunction was analyzed and results demonstrated that NK and T cells were lose their viability on dose and time dependent manner. Also, flow cytometry analysis revealed that H2O2 significantly suppresses the activation and proliferation CD8 T cell population. Whereas, NK cell subset (CD56bright and CD56dim) was dramatically altered by H2O2. When exposed to H2O2, CD56dim population was considerably increased at different time points. Hence, we conclude that H2O2 directly or functionally defect the NK and T cell mediated cytotoxicity and however, further studies are warranted to confirm the concept with mild dose of H2O2 with different cancer cell lines.
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