共查询到10条相似文献,搜索用时 359 毫秒
1.
Westermann J Reich G Kopp J Haus U Dörken B Pezzutto A 《Cancer immunology, immunotherapy : CII》2001,49(11):613-620
Granulocyte/macrophage-colony-stimulating factor (GM-CSF) plays a central role in the differentiation and function of dendritic
cells, which are crucial for the elicitation of MHC-restricted T cell responses. Preclinical and the first clinical data provide
a rationale for the application of GM-CSF in immunotherapy of cancer. Ten patients with renal cell carcinoma stage IV (Holland/Robson)
were treated in this pilot study. Therapy was started with GM-CSF alone (2 weeks). Interleukin (IL-2) and interferon α (IFNα)
were added sequentially (3 weeks GM-CSF plus IL-2 or IFNα, 3 weeks GM-CSF plus IL-2 plus IFNα). Therapy was performed on an
outpatient basis. The cytokine regimen was evaluated for toxicity, clinical response and immunomodulatory effects [fluorescence-activated
cell sorting analysis of peripheral blood mononuclear cells (PBMC), mixed-lymphocyte reaction and cytotoxicity of PBMC]. GM-CSF
treatment caused a significant increase in the number of PBMC expressing costimulatory molecules. Addition of IL-2 and IFNα
led to an increase in CD3+, CD4+, CD8+ and CD56+ PBMC in week 9. In an autologous mixed-lymphocyte reaction a 2.1-fold increase in T cell proliferation was observed after
2 weeks of GM-CSF treatment, and cytotoxicity assays showed changes in natural-killer- (NK)- and non-NK-mediated cytotoxicity
in some patients. Two patients achieved partial remission, one patient had a mixed response. The toxicity of the regimen was
mild to moderate with fever, flu-like symptoms and nausea being observed in most patients. Severe organ toxicity was not observed.
We conclude that GM-CSF might be useful for immunotherapy of renal cell carcinoma, especially in combination with T-cell-active
cytokines. Further studies are warranted.
Received: 16 March 2000 / Accepted: 10 August 2000 相似文献
2.
A group of 222 patients suffering from cellular immunodeficiency (CID), frequently combined with chronic fatigue syndrome
(CFS) and/or chronic viral infections by Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), were immunologically investigated
and treated with transfer factor (TF). The age range was 17–77 years. In order to elucidate the influence of aging on the
course of the disease and on treatment, 3 subgroups were formed: 17–43 years, 44–53 years, and 54–77 years. Six injections
of Immodin (commercial preparation of TF by SEVAC, Prague) were given in the course of 8 weeks. When active viral infection
was present, IgG injections and vitamins were added. Immunological investigation was performed before the start of therapy,
and subsequently according to need, but not later than after 3 months.
The percentages of failures to improve clinical status of patients were in the individual subgroups, respectively: 10.6%,
11.5% and 28.9%. The influence of increasing age on the percentage of failures to normalize low numbers of T cells was very
evident: 10.6%, 21.2% and 59.6%. In individuals uneffected by therapy, persistent absolute lymphocyte numbers below 1,200
cells were found in 23.1%, 54.5% and 89.3% in the oldest group. Statistical analysis by Pearson’s Chi-square test, and the
test for linear trend proved that the differences among the individual age groups were significant. Neither sex, nor other
factors seemed to influence the results.
The results of this pilot study show that age substantially influences the failure rate of CID treatment using TF. In older
people, it is easier to improve the clinical condition than CID: this may be related to the diminished number of lymphocytes,
however, a placebo effect cannot be totally excluded. 相似文献
3.
Yamamoto N Suyama H Nakazato H Yamamoto N Koga Y 《Cancer immunology, immunotherapy : CII》2008,57(7):1007-1016
Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF
precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated
by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted
to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase
generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans.
Macrophages treated with GcMAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety
of cancers indiscriminately. Administration of 100 nanogram (ng)/human maximally activates systemic macrophages that can kill
cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly
to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts
of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely
their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was
used as a prognostic index for time course analysis of GcMAF therapy. After 32–50 weekly administrations of 100 ng GcMAF,
all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of
metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase,
indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients. 相似文献
4.
Antigen-nonspecific CD8+ T suppressor cells, which suppressed delayed-type hypersensitivity (DTH) against sheep red blood cells in BALB/c mice, were induced by incubating spleen cells from mice treated with 7,12-dimethylbenz[a]anthracene (DMBA), a tumor initiator, with 12-O-tetradecanoylphorbol 13-acetate (TPA), a tumor promoter. The optimal condition was incubation in 3.2 x 10(-8) mol/5 ml of TPA for 4 days. It was shown that induction of the suppressor cells required macrophages from mice treated with DMBA. These data were consistent with the results of previous work, in which CD8+ suppressor cells were induced by painting BALB/c mice with TPA following DMBA treatment. DTH was suppressed in the culture supernatants of spleen cells from mice treated with DMBA and TPA; the suppression was genetically unrestricted. The suppressor factor was resistant to trypsin and sensitive to heating at 56 degrees C for 30 min and had affinity for the macrophages. 相似文献
5.
Dr. Giancarlo Pizza Francesco Chiodo Vincenzo Colangeli Francesco Gritti Enzo Raise Hugh H. Fudenberg Caterina De Vinci Dimitri Viza 《Biotherapy》1996,9(1-3):41-47
Twenty five HIV-1-infected patients, at various stages (CDC II, III and IV) were treated orally with HIV-1-specific transfer
factor (TF) for periods varying from 60 to 1870 days. All patients were receiving antiviral treatments in association with
TF. The number of lymphocytes, CD4 and CD8 subsets were followed and showed no statistically significant variations. In 11/25
patients the number of lymphocytes increased, whilst in 11/25 decreased; similarly an increase of the CD4 lymphocytes was
observed in 11/25 patients and of the CD8 lymphocytes in 15/25. Clinical improvement or a stabilized clinical condition was
noticed in 20/25 patients, whilst a deterioration was seen in 5/25. In 12/14 anergic patients, daily TF administration restored
delayed type hypersensitivity to recall antigens within 60 days. These preliminary observations suggest that oral HIV-specific
TF administration, in association with antiviral drugs, is well tolerated and seems beneficial to AIDS patients, thus warranting
further investigation. 相似文献
6.
Flávia Gomes de Góes Rocha Karen Cristina Barbosa Chaves Roger Chammas Jean Pierre Schatzmann Peron Luiz Vicente Rizzo Nestor Schor Maria Helena Bellini 《Cancer immunology, immunotherapy : CII》2010,59(9):1357-1365
We investigated whether the administration of IL-2 combined with endostatin gene therapy was able to produce additive or even
synergistic immunomodulatory activity in a mouse model of metastatic renal carcinoma. Renca cells were injected into the tail
vein of BALB/c mice. After 24 h, the animals were randomly divided into four groups (5 mice/group). One group of mice was
the control, the second group received treatment with 100,000 UI of Recombinant IL-2 (Proleukin, Chiron) twice a day, 1 day
per week during 2 weeks (IL-2), the third group received treatment with a subcutaneous inoculation of 3.6 × 106 endostatin-producing cells, and the fourth group received both therapies (IL-2 + ES). Mice were treated for 2 weeks. In the
survival studies, 10 mice/group daily, mice were monitored daily until they died. The presence of metastases led to a twofold
increase in endostatin levels. Subcutaneous inoculation of NIH/3T3-LendSN cells resulted in a 2.75 and 2.78-fold increase
in endostatin levels in the ES and IL-2 + ES group, respectively. At the end of the study, there was a significant decrease
in lung wet weight, lung nodules area, and microvascular area (MVA) in all treated groups compared with the control group
(P < 0.001). The significant difference in lung wet weight and lung nodules area between groups IL-2 and IL-2 + ES revealed
a synergistic antitumor effect of the combined treatment (P < 0.05). The IL-2 + ES therapy Kaplan–Meier survival curves showed that the probability of survival was significantly higher
for mice treated with the combined therapy (log-rank test, P = 0.0028). Conjugated therapy caused an increase in the infiltration of CD4, CD8 and CD49b lymphocytes. An increase in the
amount of CD8 cells (P < 0.01) was observed when animals received both ES and IL-2, suggesting an additive effect of ES over IL-2 treatment. A synergistic
effect of ES on the infiltration of CD4 (P < 0.001) and CD49b cells (P < 0.01) was also observed over the effect of IL-2. Here, we show that ES led to an increase in CD4 T helper cells as well
as cytotoxic lymphocytes, such as NK cells and CD8 cells, within tumors of IL-2 treated mice. This means that ES plays a role
in supporting the actions of T cells. 相似文献
7.
Summary. Previous investigations showed an impairment of amino acids (AA) metabolism in amyotrophic lateral sclerosis (ALS). It was
hypothesized that excitatory AA may play an important role in the etiopathogenesis of this disease. The aim of the study was
to determine plasma AA concentrations in ALS patients, and to examine the relationship between AA and the clinical state of
ALS patients, the type of ALS onset and the duration of the disease. The study involved 20 ALS patients and 30 control group
people. The AA analysis was performed by ion – exchange chromatography on an automatic AA analyser. The results showed significantly
decreased concentrations of valine, isoleucine, leucine, tyrosine and aspartate in the plasma of the whole group of ALS patients
compared to the control group, and a significantly decreased concentration of arginine in the patients with a long duration
of ALS compared to the patients with a short duration. The clinical state of ALS patients significantly influenced only plasma
alanine concentration. Other plasma AA concentrations were not significantly associated with clinical parameters of the disease.
Our study confirms that metabolic abnormalities concerning AA exist in ALS patients. However, the normal plasma glutamate
concentration observed in this study in the whole group of ALS patients compared to the controls does not exclude that this
excitatory AA may play a role in neurodegeneration in ALS.
Received June 22, 2002 Accepted October 3, 2002 Published online January 23, 2003
Correspondence: Joanna Iłżecka M.D., Department of Neurology, Medical University, Jaczewskiego 8, 20-954 Lublin, Poland,
Fax: +48 81 742 55 34, E-mail: Ilzecka@medscape.com 相似文献
8.
P. De Paoli E. Vaccher R. Tedeschi C. Caffau S. Zanussi M. T. Bortolin C. Crepaldi M. Spina U. Tirelli 《Cancer immunology, immunotherapy : CII》2001,50(3):157-162
The anti-CD20 monoclonal antibody Rituximab is a novel antitumor agent used in association with chemotherapy (CT) for the
treatment of high-grade/intermediate non-Hodgkin's lymphomas (NHL) in HIV-negative populations. This therapeutic combination
is currently also being explored in HIV-positive patients with NHL (HIV-NHL). The objective of our study was to determine
CD4 and CD8T cell counts, HIV plasma viremia and proviral load in patients with CD20-positive HIV-NHL treated with Rituximab
plus CT and highly active antiretroviral therapy (HAART). We studied eight patients with HIV-NHL treated by anti-CD20 and
CT before, after three, and after six cycles of therapy; CD4, CD8 and CD19 lymphocyte subsets were measured by monoclonal
antibodies and flow cytometry. HIV plasma viremia was determined by the b-DNA assay, and proviral load by a quantitative competitive
PCR. CD4T cell counts remained stable after three cycles of therapy, while a significant reduction of this subset was present
at the end of therapy. HIV plasma viremia was significantly reduced after the third cycle, but returned to pretreatment levels
at the end of therapy; we also observed individual fluctuations of proviral load during therapy, this marker being increased
in two out of three patients at the end of therapy. These observations suggest that Rituximab plus CT accelerated the rate
of CD4 depletion and of HIV replication in the peripheral blood of HIV-NHL patients and that HAART may be able to delay these
effects.
Received: 1 December 2000 / Accepted: 8 February 2001 相似文献
9.
Pullarkat V Deo Y Link J Spears L Marty V Curnow R Groshen S Gee C Weber JS 《Cancer immunology, immunotherapy : CII》1999,48(1):9-21
A phase I study of escalating doses of humanized bispecific antibody (bsAb) MDX-H210 with granulocyte-colony-stimulating
factor (G-CSF) was conducted in patients with metastatic breast cancer that overexpressed HER2/neu. The main objectives of
the study were to define the maximal tolerated dose (MTD) of MDX-H210 when combined with G-CSF, to measure the pharmacokinetics
of MDX-H210 when administered with G-CSF, and to determine the toxicity, biological effects and possible therapeutic effect
of MDX-H210 with G-CSF. MDX-H210 is a F(ab)′ × F(ab)′ humanized bispecific murine antibody that binds to both HER2/neu and
the FcγR1 receptor (CD64), and was administered intravenously weekly for three doses followed by a 2-week break and then three
more weekly doses. A total of 23 patients were treated, and doses were escalated from 1 mg/m2 to 40 mg/m2 with no MTD reached. The toxicity of the bsAb + G-CSF combination was modest, with no dose-limiting toxicity noted: 19 patients
had fevers, 7 patients had diarrhea, and 3 patients had allergic reactions that did not limit therapy. The β-elimination half-life
varied from 4 h to 8 h at doses up to 20 mg/m2. Significant release of cytokines interleukin-6, G-CSF, and tumor necrosis factor α was observed after administration of
bsAb. Circulating monocytes disappeared within 1 h of bsAb infusion, which correlated with binding of bsAb, noted by flow-cytometric
analysis. Significant levels of human anti-(bispecific antibody) were measured in the plasma of most patients by the third
infusion. No objective clinical responses were seen in this group of heavily pre-treated patients.
Received: 23 July 1998 / Accepted: 6 November 1998 相似文献
10.
Regulatory T cells prevent autoimmunity by suppressing the reactivity of potentially aggressive self-reactive T cells. Contact-dependent CD4+ CD25+ 'professional' suppressor cells and other cytokine-producing CD4+ and CD8+ T-cell subsets mediate this protective function. Evidence will be reviewed that T cells primed with transforming growth factor (TGF)-beta expand rapidly following restimulation. Certain CD4+ T cells become contact-dependent suppressor cells and other CD4+ and CD8+ cells become cytokine-producing regulatory cells. This effect is dependent upon a sufficient amount of IL-2 in the microenvironment to overcome the suppressive effects of TGF-beta. The adoptive transfer of these suppressor cells generated ex vivo can protect mice from developing chronic graft-versus-host disease with a lupus-like syndrome and alter the course of established disease. These data suggest that autologous T cells primed and expanded with TGF-beta have the potential to be used as a therapy for patients with systemic lupus erythematosus and other chronic inflammatory diseases. This novel adoptive immunotherapy also has the potential to prevent the rejection of allogeneic transplants. 相似文献