scholarly journals Induction of CD4+Leu 8- lymphokine-activated killer (LAK) cells by recombinant interleukin 2 in gastric cancer patients, and augmentation of LAK cell activities by addition with exogeneous recombinant interferon .GAMMA. and immunological phenotypic analysis of the cells.

1989 ◽  
Vol 12 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Tsugio Ebihara ◽  
Shohei Koyama ◽  
Katashi Fukao ◽  
Toshiaki Osuga
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Interferon Gamma ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Phenotypic Analysis ◽  
Recombinant Interferon ◽  
Lak Cell ◽  
Recombinant Interleukin 2 ◽  
Gastric Cancer Patients

A phase I trial of recombinant interleukin-2 combined with recombinant interferon-gamma in patients with cancer.

1990 ◽  
Vol 8 (7) ◽  
pp. 1269-1276 ◽  
Author(s):  
B G Redman ◽  
L Flaherty ◽  
T H Chou ◽  
A al-Katib ◽  
M Kraut ◽  
...  
Keyword(s):  
Phase I ◽  
Interferon Gamma ◽  
Phase I Trial ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Ifn Gamma ◽  
Recombinant Interferon ◽  
Lak Cell ◽  
Recombinant Interleukin 2 ◽  
Lak Cell Activity

Twenty-six patients with metastatic cancer were entered into a phase I trial of concurrent recombinant interleukin-2 (IL-2) and recombinant interferon-gamma (IFN-gamma). IL-2 was administered as a continuous intravenous infusion for 5 days. IFN-gamma was administered by a daily intramuscular (IM) injection during the 5 days of IL-2 administration. Treatment was repeated twice after 9-day rest periods. After a 2-week rest, patients without evidence of tumor progression were retreated. Natural killer (NK)- and lymphokine-activated killer (LAK)-cell activity were assayed in each patient before treatment, on day 1, and on day 5 of each cycle. Constitutional symptoms occurred in most patients but were not dose-limiting. Other toxicities included hypotension responsive to fluids, transient elevations in liver function tests, erythema/pruritus, eosinophilia, and transient leukopenia/thrombocytopenia. The maximum-tolerated dose (MTD) of the combination was 1 x 10(6) U/m2/d of IL-2 combined with 0.50 mg/m2/d of IFN-gamma. The dose-limiting toxicity was pulmonary manifesting as rales and shortness of breath. The dose of the combination that resulted in the optimal generation of in vivo LAK-cell activity was a dose of at least 0.25 mg/m2/d of IFN-gamma combined with 1 x 10(6) U/m2/d of IL-2. Objective clinical responses were seen in five of 26 patients. These included a partial response of 2 months duration in a patient with non-Hodgkin's lymphoma (NHL), mixed responses in a patient with NHL and two patients with renal cell carcinoma (RCC), and an ongoing assessable response in a patient with bone metastases from RCC. The recommended dose for phase II trials of this combination is 0.50 mg/m2 of IFN-gamma and 1 x 10(6) U of IL-2.

Subcutaneous Therapy with Low-Dose Interleukin-2 plus the Neurohormone Melatonin in Metastatic Gastric Cancer Patients with Low Performance Status

1993 ◽  
Vol 79 (6) ◽  
pp. 401-404 ◽  
Author(s):  
Paolo Lissoni ◽  
Fernando Brivio ◽  
Antonio Ardizzoia ◽  
Gabriele Tancini ◽  
Sandro Barni
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Low Dose ◽  
Tumor Regression ◽  
Performance Status ◽  
Interleukin 2 ◽  
Biological Response ◽  
Metastatic Gastric Cancer ◽  
Low Performance ◽  
Gastric Cancer Patients

Aims and background Patients with disseminated gastric cancer are generally in very bad clinical conditions, which make them not eligible for potentially active polychemotherapies. This justifies the development of less toxic therapies such as the use of biological response modifiers. Unfortunately, IL-2, one of the most promising cytokines, does not seem to be effective in gastric cancer. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify IL-2 activity, which becomes biologically effective also at very low doses. Based on these considerations, a pilot study was performed with low-dose subcutaneous IL-2 in combination with MLT in metastatic gastric cancer patients with low performance status. Methods The study included 14 patients with metastatic gastric cancer who received IL-2 at a dose of 3 million IU/day at 8.00 p.m. subcutaneously for 6 days/week for 4 weeks. MLT was given orally at a dose of 50 mg/day at 8.00 p.m. every day starting 7 days before IL-2. In patients in whom the disease did not progress, a second cycle was given after a rest period of 21 days. Results A tumor regression was obtained in 3/14 (21 %) patients, complete response in 1 and partial in 2, with a median duration of 13+ months. The disease stabilized in 6/14 (43 %) patients and progressed in the remaining 5 (36 %). Survival was significantly longer in patients with response or stable disease than in those with progression. Toxicity was low in all cases. Conclusions These preliminary results show that the combination on of low-dose subcutaneous IL-2 and the pineal hormone MLT may represent a new well tolerated biotherapy, capable of inducing objective tumor regression also in patients with metastatic gastric cancer and low performance status.

Intralesional Infusion of Lymphokine-activated Killer (LAK) Cells and Recombinant Interleukin-2 (rIL-2) for the Treatment of Patients with Malignant Brain Tumor

Neurosurgery ◽  
1988 ◽  
Vol 23 (6) ◽  
pp. 725-732 ◽  
Author(s):  
Randall E. Merchant ◽  
Lynn H. Merchant ◽  
Sallie H. S. Cook ◽  
Daniel W. McVicar ◽  
Harold F. Young
Keyword(s):  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Treatment Protocol ◽  
Lak Cells ◽  
Ct Scans ◽  
Computed Tomographic ◽  
Lak Cell ◽  
Recombinant Interleukin 2

Abstract Twenty patients with supratentorial, intracerebral lesions defined by computed tomographic scan or magnetic resonance imaging were treated by surgery and adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant Interleukin-2 (rIL-2, Cetus). Seventeen patients had glioblastoma, two had high-grade oligodendroglioma, and one patient had two metastatic sarcoma lesions. LAK cells were produced from blood mononuclear cells (MNC) obtained by 2 to 3 leukapheresis procedures and cultured (2.5 × 106 MNC/ml) 3 to 5 days with 1000 units rIL-2/ml. Although LAK cells could be produced from MNC of all patients, those taking steroids or with a low Karnofsky functional status generated, on average, suboptimal LAK cell activity. Age, sex, and serum anticonvulsant levels do not seem to influence a patient's ability to produce LAK cells in vitro. For therapy, cultured MNC (1-15 × 109) containing LAK cells were suspended in saline containing 106 units rIL-2 and injected into tissue surrounding the tumor cavity during craniotomy. For 3 days after their operations, patients received 106 units rIL-2 into the tumor cavity through an Ommaya reservoir. The treatment protocol was tolerated well by all patients, although they all experienced some degree of headache, fever, or lethargy that cleared within a few days of the last rIL-2 injection. When computed tomographic (CT) scans were obtained soon after treatment, areas of low density suggested a greater-than-normal extent of edema around the operative site. At the present time, CT scans indicate that the tumors of seven patients have recurred with an average disease-free interval of 25 ± 6 weeks. Eight patients have remained alive and free of tumor for at least 6 months after surgery and immunotherapy. LAK cell plus rIL-2 immunotherapy for brain tumors is safe and may be efficacious against minimal tumor burden.

scholarly journals Stimulatory role of interleukin 10 in CD8+ T cells through STATs in gastric cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770620 ◽  
Author(s):  
Jianjun Xi ◽  
Mingzheng Xu ◽  
Zongchang Song ◽  
Hongqiang Li ◽  
Shumin Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Patients ◽  
Interferon Gamma ◽  
Interleukin 10 ◽  
Receptor Expression ◽  
Cancer Stage ◽  
Signal Transducer ◽  
Gastric Cancer Patients

CD8+ T cells are considered to be critical in tumor surveillance and elimination. Increased CD8+ T cell frequency and function is associated with better prognosis in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8+ T cell–mediated anti-tumor immunity. We therefore examined the interleukin 10 expression and consumption in CD8+ T cells harvested from the peripheral blood and resected tumors of gastric cancer patients of stages II–IV. We found that the gastric cancer patients presented significantly elevated frequencies of interleukin 10–expressing cells in both CD4+ and CD8+ T cells compared to healthy controls. But distinctive from the interleukin 10–expressing CD4+ T cells, which increased in frequency in advanced cancer, the interleukin 10–expressing CD8+ T cells did not increase with cancer stage in the peripheral blood and actually decreased with cancer stage in resected tumor. Interleukin 10 and interleukin 10 receptor expression was also enriched in interferon gamma–expressing activated CD8+ T cells. Compared to interleukin 10–nonexpressing CD8+ T cells, interleukin 10 receptor–expressing CD8+ T cells secreted significantly elevated interferon gamma levels. Treatment of anti-CD3/CD28-stimulated, purified CD8+ T cells with interleukin 10 alone could significantly enhance CD8+ T cell survival, an effect dependent on interleukin 10 receptor expression. Interleukin 10 also increased CD8+ T cell proliferation synergistically with interferon gamma but not alone. Analysis of downstream signal transducer and activator of transcription molecules showed that interleukin 10 treatment significantly increased the phosphorylation of signal transducer and activator of transcription 3 and signal transducer and activator of transcription 1 to lesser extent. Together, these results demonstrate that interleukin 10 possessed stimulatory roles in activated CD8+ T cells from gastric cancer patients.

Phase IB study on prevention of surgery-induced immunodeficiency with preoperative administration of low-dose subcutaneous interleukin-2 in gastric cancer patients

2001 ◽  
Vol 78 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Katia Cerea ◽  
Fabrizio Romano ◽  
Andrea Ferrari Bravo ◽  
Vittorio Motta ◽  
Fabio Uggeri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Low Dose ◽  
Interleukin 2 ◽  
Phase Ib ◽  
Preoperative Administration ◽  
Gastric Cancer Patients
Sign in / Sign up

Export Citation Format

Share Document