Immunotherapy Group Research Articles

Immunotherapy with the saponin enriched-Leishmune ® vaccine versus immunochemotherapy in dogs with natural canine visceral leishmaniasis

Leishmune ®, the first licensed vaccine for prophylaxis against canine visceral leishmaniasis (CVL) and is also immunotherapeutic when used with double saponin adjuvant concentration. The Leishmune ® therapeutic vaccine was assessed for immunotherapy (IT) in 31 infected dogs and for immunochemotherapy (ICT) in combination with allopurinol or amphotericinB/allopurinol, in 35 dogs. Compared to infected untreated control dogs, at month 3, both treatments increased the proportion of dogs showing intradermal response to Leishmania antigen to a similar extent (from 8 to 67%, in the IT and to 76%, in the ICT groups), and conversely reduced from 100 to 38% (IT) and to 18% (ICT) the proportion of symptomatic cases, from 54 to 12% (IT) and to 15% (ICT) the proportion of parasite evidence in lymph nodes and from 48 to 19% (IT) and 12% (ICT) the proportion of deaths, indicating that the immunotherapy with enriched-Leishmune ® vaccine promotes the control of the clinical and parasitological signs of CVL rendering most dogs asymptomatic although PCR positive. By month 8, negative lymph node PCR results were obtained in 80% of the ICT-treated dogs, but only in 33% of the IT group ( p = 0.0253), suggesting that the combination of additional chemotherapy with Leishmune ®-enriched saponin vaccination abolished, not only the symptoms but also the latent infection condition, curing the dogs. The animals were followed up until 4.5 years after the beginning of the experiment and, compared to the untreated control group at month 3 (12/25 dogs; 48%), a decrease in the rate of CVL deaths was only seen after ICT treatment (7/35 dogs; 20%; 0.0273) but not after IT treatment (10/31 dogs; 32%; p = 0.278), pointing out an additional advantage of the ICT treatment with the enriched-Leishmune ® in the control and cure of CVL.

Assessment of the value of leukocyte immunization in vitro fertilization-embryo transfer (IVF-ET)

OBJECTIVE: To investigate the value of leukocyte immunization in vitro fertilization-embryo transfer(IVF-ET) programme. DESIGN: The IVF-ET outcomes were compared between two groups with or without leukocyte immunization treatment. MATERIALS AND METHODS: Blocking antibody level was determined by complement-dependent cytotoxic test in patients with tubal infertility accompanying with history of spontaneous abortion or spontaneous abortion after IVF-ET, and leukocyte immunization was performed in 36 patients with negative blocking antibody, and the IVF-ET outcomes were compared with 42 patients without leukocyte immunization treatment as the control group. RESULTS: 45 IVF-ET cycles in the immunotherapy group gave rise to 23 pregnancies, and 47 IVF-ET cycles in the control group gave rise to 21 pregnancies. The spontaneous abortion rates of the immunotherapy group and the control group were 13.04%(3/23) and 38.10%(8/21) respectively, and the success rates of pregnancy in the two groups were 86.96%(20/23) and 57.14%(12/21) respectively (P<0.05). CONCLUSIONS: Leukocyte immunization is effective in patients with history of spontaneous abortion or spontaneous abortion after IVF-ET and absence of blocking antibody in IVF-ET programme.

Clinico-immunologic Study on Immunotherapy with Mixed and Single Insect Allergens

Immunotherapy (IT) is practiced mainly with mixed and single allergen vaccines. But studies are rare with mixed allergen preparations. The objective of this study is to study mix and single insect allergen IT in patients of allergic rhinitis and asthma. We performed a double-blind placebo-controlled trial of mix and single allergen IT for 1 year in 99 patients of asthma or rhinitis or both. There were two groups, (1) active allergen IT (n = 61) with three subgroups single insect extract (cockroach, housefly, or mosquito) and mix allergen IT (two or three insect extracts) and (2) placebo (n = 38). Clinical (skin reactivity, airway reactivity, and symptom score) and immunological (IgE/IgG4 and IgG1/IgG4 ratio) parameters were assessed at baseline and after 1 year of IT. Eighty-five patients completed 1 year of IT. The active allergen IT group patients showed a significant improvement compared to baseline values (p < 0.05) and placebo group patients (p < 0.05) with regard to symptom scores, FEV1 values, and immunological parameters (IgG4). No significant difference was found between mixed and single IT group patients for changes in clinical and immunological parameters. Positive correlation was observed between increase in IgG4 and clinical improvement. The changes in above parameters in placebo group were nonsignificant after 1 year of treatment. IT with two to three mix extract from the same allergen group is effective for insect hypersensitivity.

Immunotherapy for cure and prophylaxis of allergic rhinitis

SummaryThe possible cure of Japanese cedar pollen‐induced allergic rhinitis (AR) by immunotherapy was investigated. The mechanism of cure was also studied from the viewpoint of the T cell response to allergen; it was documented that absence of IL‐5 production from allergen‐stimulated T cells was the major mechanism. The prophylactic aspect of immunotherapy was also investigated. Eighty‐eight asymptomatic subjects who were already sensitized to pollen were recruited. Of these subjects, 31 (prophylactic immunotherapy group) were treated with pollen immunotherapy for 3 years. The remaining 57 individuals (control group) were not treated with pollen immunotherapy. At the end of the 3‐year trial, only 28 of 57 individuals (49.1%) in the control group remained asymptomatic. On the other hand, 27 of 31 individuals (87.1%) in the prophylactic immunotherapy group remained asymptomatic. Prophylactic immunotherapy decreased IL‐4 synthesis from pollen allergen‐stimulated T cells, suggesting that this was the mechanism of prevention of symptoms' outbreak. We next examined whether mite immunotherapy for patients monosensitized to mite allergen could prevent new sensitization to pollens. A total of 132 patients monosensitized to house dust mites were included. Of these individuals, 52 (pharmacotherapy group) were treated with antihistamine tablets for 4 years, and the remaining 80 patients (mite immunotherapy group) were treated with mite immunotherapy for the same time period. Whereas 15 of 52 patients (28.8%) in the pharmacotherapy group attained new sensitization to some kinds of pollen allergens, only five of 80 patients (6.3%) in the mite immunotherapy group attained new sensitization. Our data suggest that mite immunotherapy can prevent new sensitization to pollen allergens. It is therefore concluded that pollen immunotherapy cannot only cure pollen‐induced AR but also prevent outbreaks of pollen‐induced AR, and that mite immunotherapy can prevent new sensitization to pollen allergens.

Frequency of imported fire ant stings in patients receiving immunotherapy

Imported fire ant (IFA) stings are an important cause of stinging insect hypersensitivity in endemic areas. IFA stings are difficult to avoid, and many studies have shown high field sting rates. No studies report the natural IFA sting rate that patients experience while receiving IFA immunotherapy. To determine the frequency of IFA stings in patients receiving IFA immunotherapy compared with an aeroallergen immunotherapy control group. Patients were surveyed by telephone to characterize the frequency of stings, reactions, and attitudes toward IFA avoidance. A total of 23 of 28 patients reported IFA stings during their IFA immunotherapy compared with 16 of 28 patients during their aeroallergen immunotherapy. More of the IFA immunotherapy-treated patients were stung than the aeroallergen immunotherapy patients, which is inconsistent with our hypothesis (chi2 = 4.139, P < .042). The annualized sting rates between the IFA immunotherapy and aeroallergen immunotherapy groups were similar (1.82 vs 1.72 stings per year, P < .55). The IFA immunotherapy patients were more likely to report any kind of reaction (chi2 = 9.124, P < .003) compared with the control group. Most patients reported feeling careful to avoid stings. Patients with IFA hypersensitivity treated with IFA immunotherapy do not experience a decreased frequency of stings resulting from attention to sting avoidance. IFA stings are frequent and difficult to avoid. Rush IFA immunotherapy is a good option for many patients to achieve protection quickly.

Cytokine profiles of HIV patients with pulmonary tuberculosis resulting from adjunct immunotherapy with herbal phytoconcentrates Dzherelo and Anemin

Dzherelo (Immunoxel) and Anemin when combined with standard anti-tuberculosis therapy (ATT) were shown to produce better clinical outcome than chemotherapy alone. Sixty HIV-positive patients with active pulmonary TB were equally divided into three matched groups to receive either ATT, ATT + Dzherelo, or ATT + Dzherelo + Anemin. Peripheral blood samples were measured by ELISA for plasma levels of IL-2, IL-6, TNF-α, IFN-γ, and IFN-α. After 6 months of follow-up Dzherelo and Dzherelo + Anemin combinations produced 61% ( P = 0.005) and 44.4% ( P = 0.06) higher levels of IL-2, whereas in ATT group they were reduced by 33.1% ( P = 0.002). The levels of IL-6 increased by 17% ( P = 0.15) in ATT group, but declined in both immune intervention groups by 26.2% ( P = 0.007) and 21.3% ( P = 0.22). TNF-α was suppressed in two immunotherapy groups by 19.1% ( P = 0.06) and 76.3% ( P = 0.02), respectively, but had risen by 14% ( P = 0.42) in ATT patients. The pattern of production of IFN-γ was opposite to that of TNF-α, but statistical significance was stronger in patients receiving ATT and Dzherelo + Anemin than in Dzherelo group: −34% ( P = 0.004), +31.9% ( P = 0.008), and +17.3% ( P = 0.33), respectively. Moderately decreased levels of IFN-α were observed in all treatment arms (range 0.9–16.6%) but differences were not significant. Despite considerable intra-group variation in cytokine production, the baseline inter-group averages were not statistically different indicating that the results were not biased by sample heterogeneity. Immunomodulators used in this study possibly act by enhancing natural immune response against TB. Expanded study of other cytokines and correlates relevant to control and protection from TB and HIV is needed in order to identify biomarkers of favorable treatment outcome, which may aid design of better immune interventions and vaccines.

Transfer of T cells from intranasal ovalbumin-immunized mice ameliorates allergic response in ova-sensitized recipient mice

Mucosal immunotherapy is suggested as a treatment strategy for tolerance induction in allergic diseases. The purpose of this study was to determine the effect of transferred splenic T cells from intranasal ovalbumin (OVA)-immunized mice to naive mice before sensitization on its impact of cytokine production and airway histopathology. BALB/c mice in group I received intranasal immunotherapy (days1-6), carboxylfluorescein succinyl ester (CFSE)-labeled splenocytes or splenic T cells were i.v. transferred to naive recipients (group II) before OVA sensitization. Acute murine asthma model was established by two i.p. OVA injections (days 21 and 28) and seven OVA nebulizations (days 42-48) in groups I, II and III. Groups III and IV served as asthma model and control, respectively. CFSE-labeled cells in splenocytes and lymph node lymphocytes, lung histopathology, IL-4, IL-10, and interferon (IFN) gamma cytokines of recipients were analyzed 24 hours after OVA nebulization challenge. CFSE-labeled T cells from group I were detected in spleen and regional lymph nodes of the OVA-sensitized recipients (group II). Smooth muscle and thickness of airways were less in intranasal OVA immunotherapy and OVA-sensitized recipients when compared with the asthma model (p < 0.05). Area of inflammation was significantly suppressed in OVA-sensitized recipients compared with the asthma model (p < 0.01). IL-10 and IFN-gamma levels in splenocyte supernatants were significantly increased in intranasal immunotherapy and OVA-sensitized recipients compared with asthma model and controls (p < 0.01). IL-4 levels were significantly less in intranasal immunotherapy group and the OVA-sensitized recipient group when compared with asthma the model group (p < 0.05). This study suggests that intranasal immunotherapy with allergens regulates T-cell responses and ameliorates airway histopathology in sensitized mice, hence, encouraging mucosal tolerance induction as a suitable treatment of allergic diseases.

Quantitation of canine regulatory T cell populations, serum interleukin-10 and allergen-specific IgE concentrations in healthy control dogs and canine atopic dermatitis patients receiving allergen-specific immunotherapy

Canine atopic dermatitis (AD) shares many clinical and immunological similarities with human AD. Regulatory T cells (Treg) are a distinct lineage of T lymphocytes with various immunosuppressive properties including the down-regulation of allergic inflammation associated with IgE production. Antigen-induced Treg typically regulate immune homeostasis via productions of cytokines such as interleukin-10. Given the immunological similarities with human AD, it is likely that Tregs and the cytokines they produce play an important role in diseases of dogs as well. A cross-reactive FoxP3 antibody was used to identify a subset of CD4 + T cells in the blood of both healthy dogs and dogs with atopic dermatitis undergoing immunotherapy over a year period. There was no significant difference in the Treg percentage over time in the healthy dogs. The immunotherapy group showed a significant increase in Treg percentage at 6, 9, and 12 months when compared to the healthy dogs. For the immunotherapy group, the mean Treg percentage at the beginning of the study was 4.94 ± 0.71 and 10.86 ± 2.73 at the completion. A commercially available ELISA kit was also used to quantitate the concentration of IL-10 in the serum of the same subsets of dogs. There was no significant difference in the IL-10 concentrations over time in the healthy dogs. The immunotherapy group showed a significant increase in serum IL-10 concentrations at 6, 9, and 12 months when compared to the control group. The mean serum IL-10 concentration at the initiation of immunotherapy was 20.40 ± 3.52 ng L −1 and 37.26 ± 15.26 ng L −1 at the completion of the study. The immunotherapy group also showed a significant decrease in serum IgE levels over the 1-year treatment period for specific allergens identified during ASIT. We conclude from these studies that similar to humans undergoing immunotherapy, increasing Treg populations likely play a significant role in the success of this particular type of therapy for atopic dermatitis and other allergic conditions.

Immunotherapeutic efficacy of BCG vaccine in pulmonary tuberculosis and its preventive effect on multidrug-resistant tuberculosis

To evaluate the effect and safety of BCG vaccine on initially treated pulmonary tuberculosis and its controlling effect on multidrug-resistant tuberculosis. All 360 volunteers with initially treated pulmonary tuberculosis of positive smear and culture were divided into immunotherapy group (180 cases, also BCG group) and control group (180 cases) at random pair. The patients in BCG group were treated with chemotherapy of a regimen of 2HRZ/2HR and immunotherapy with BCG for 4 months,and the first BCG vaccine was given a month after chemotherapy. Meanwhile, the patients in the control group were treated with chemotherapy of 2HRZ/4HR only. (1) The negative conversion rate of sputum smear in BCG group was 98.3% (177/180), and it was 97.2% (175/180) in control group. There was no significant difference between the two groups both at the ends of 4 and 6 months after treatment (chi2 = 0.1278, P > 0.05). (2) The positive conversion rate of sputum smear in BCG group was 2.3% (4/177), and it was 6.9% (12/175) in control group followed up for 5 years. The successful rate was 96.1% (173/180) in BCG group, and it was significantly higher than that of 90.6% (163/180) in control group (chi2 = 4.4643, P < 0.05). (3) In the 5-year follow up, bacteriologic result was similar to that of X-ray. (4) The occurrence rate of multidrug-resistant tuberculosis was 2.3% (4/177) in BCG group,significantly lower than that of 7.3% (13/178) in the control group (chi2 = 4.9513, P < 0.05). As an adjunct chemotherapy,immunotherapy with BCG vaccine should be helpful for patients with initially treated pulmonary tuberculosis. It would further strengthen the effects of chemotherapy and reduce the occurrence rate of multidrug-resistant tuberculosis.

Double‐blind, placebo‐controlled Alternaria alternata immunotherapy: in vivo and in vitro parameters

Few studies have been published on the efficacy and safety of immunotherapy with fungal extracts, possibly because of difficulties arising from antigenic variability among different strains of fungus. The aim of the study was to analyze changes in the in vivo and in vitro parameters in response to immunotherapy with an Alternaria alternata extract. We studied 28 patients with rhinitis, bronchial asthma, or both caused by Alternaria. The patients were randomized to the active immunotherapy or placebo group, and a conventional schedule of immunotherapy was used. We recorded changes for a year in skin reactivity (skin prick test), conjunctival reactivity (conjunctival provocation test), and in vitro parameters (serum-specific IgE, IgG, IgG1 and IgG4 for A. alternata complete extract and for natural and recombinant Alt a 1). Twenty-three patients completed the study and all attained the maintenance dose. There were no changes in skin reactivity in the active treatment group, and reactivity increased at the end of the study period in the placebo group. Conjunctival sensitivity decreased only in the active treatment group when the maintenance dose was reached. Allergen-specific IgE decreased, and IgG, IgG1 and IgG4 increased in all periods of study in the active treatment group, with no changes in the placebo group. Allergen-specific immunotherapy with the A. alternata extract tested here led to a decrease in conjunctival reactivity and induced a significant immunologic response.

Safety and efficacy of the ultra-rush immunotherapy with extracts of Dermatophagoides pteronyssinus in children

Purpose :Immunotherapy is accepted as the only treatment of allergic disease that can modify the natural course of the disease and ameliorate symptoms. This study aimed to evaluate the safety and efficacy of ultra-rush therapy using Dermato phagoides extracts in children. Methods :Of children older than four years who had visited Bundang CHA Pediatric Allergy Clinic, those showing positive reactions only to Dermatophagoides in the skin prick test and to the nasal provocation test were included. In all, 11 and 12 patients respectively preferred conventional and ultra-rush immunotherapy. We elevated allergen concentrations diluted to 1,000:1 of the end strength by 2-3 times with 30-minute intervals and checked oxygen saturation, pulse rate, blood pressure, and systemic reactions every 15 minutes. Immunotherapy effectiveness was valued by changes in nasal provocation test scores before and after immunotherapy. Results : The average ages of patients in the conventional and ultra-rush immunotherapy groups were 8.3±2.3 and 9.2± 2.8 years, respectively. Systemic reactions were observed in six in the ultra-rush group (50%) without anaphylaxis and one (9%) in the conventional group. The average scores in the nasal provocation test before and after treatment in the conven tional group were 8.2±1.5 and 4.6±2.1, respectively (P=0.043). In the ultra-rush immunotherapy group, the scores changed from 6.2±2.2 to 3.7±2.5 (P=0.017). Conclusion : Ultra-rush immunotherapy using Dermatophagoides in children is effective for treating allergic disease but can induce systemic effects rather than conventional immunotherapy. (Korean J Pediatr 2008;51:868-873)

Minimally Invasive Treatment Combined With Cytokine-induced Killer Cells Therapy Lower the Short-term Recurrence Rates of Hepatocellular Carcinomas

The recurrence of hepatocellular carcinoma (HCC) after minimally invasive therapy is frequent. Adoptive immunotherapy is thought to be an effective method to lower recurrence and metastasis rates of malignant tumors. Therefore, 85 HCC patients after transcatheter arterial chemoembolization and radiofrequency ablation therapy were randomized to immunotherapy group and no adjuvant therapy group. Autologous cytokine-induced killer (CIK) cells were transfused via hepatic artery to the patients. The alteration of levels of lymphocyte subsets in peripheral blood of patients was examined by flow cytometry. All patients were screened by computed tomography every 2 months to observe the tumor recurrent conditions. After CIK cell infusions, the percentages of CD3+, CD4+, CD56+, CD3+CD56+ cells, and CD4+/CD8+ ratio increased from 68.6+/-11.0%, 31.1+/-9.0%, 15.6+/-7.9%, 5.2+/-3.1%, and 1.1+/-0.5 to 70.7+/-10.1%, 33.5+/-8.0%, 18.4+/-9.4%, 5.9+/-2.8%, and 1.3+/-0.7, respectively (P<0.05); whereas the percentage of CD8 cells decreased from 31.1+/-7.8% to 28.6+/-8.3% (P<0.05). The 1-year and 18-month recurrence rates of the study group were 8.9% and 15.6%, compared with 30.0% and 40.0% of the control group (both P value<0.05). The data suggest that CIK cell transfusion is an effective treatment. It can boost the immunologic function in HCC patients and plays an important role in reducing the recurrence rate of HCC.

No role of adjuvant systemic therapy after complete metastasectomy in metastatic renal cell carcinoma?

Objective To compare the effects of metastasectomy combined with immunotherapy and metastasectomy alone in the treatment of patients with metastatic renal cell carcinoma. Materials and Methods A total of 93 patients who had undergone metastasectomy were included in the study. Patients were categorized according to immunotherapy status, including the immunotherapy group (n = 70) and the no immunotherapy group (n = 23). Results In the immunotherapy group, median overall survival was 56.1 months (95% confidence interval [CI] 34.1–78.2), whereas the no immunotherapy group reached a median overall survival of 21.3 months (95% CI 3.4–39.2), respectively. The 1, 3, and 5-year overall survival rates were calculated at 67.1% and 56.5%, 30.0% and 34.8%, and 7.1% and 19.0%, for the immunotherapy group and the no immunotherapy group, respectively ( P = 1.000). When patients were stratified according to the time of metastasis, overall survival was not significantly different among the groups in patients with synchronous metastasis or in those with metachronous metastasis. Multivariate Cox proportional hazards model analysis showed that multiplicity of metastasis (odds ratio 3.68; 95% CI 1.85–7.34; P < 0.001) and metastatic sites (odds ratio 2.12; 95% CI 1.15–3.90; P = 0.016) were independent predictors of overall survival. Conclusions Metastasectomy combined with adjuvant immunotherapy did not result in a significantly higher overall survival rate as compared with metastasectomy alone. Our findings raise the question of “Is there a role of adjuvant immunotherapy after complete metastasectomy in patients with metastatic renal cell carcinoma?”

Prospective phase II study of post-surgical adjuvant chemo-immunotherapy using autologous dendritic cells and activated killer cells from tissue culture of tumor draining lymph nodes in primary lung cancer patients

3048 Background: We conducted a phase II study to evaluate the efficacy and toxicity of adjuvant chemo-immunotherapy using dendritic cells and activated killer cells from tissue culture of tumor-draining lymph nodes (TDLN) in primary lung cancer patients. Methods: Pathological N2 lung cancer patients were selected for the post-surgical adjuvant chemo-immunotherapy. Activated killer cells and dendritic cells obtained from tissue cultures of TDLN or TDLN co-cultured with peripheral blood lymphocytes (TDLN-Pb) were used for the adoptive transfer of immunotherapy. Patients received 4 courses of post-surgical chemotherapy or chemotherapy along with immunotherapy (immunotherapy group) every 2 months for 2 years. Results: There were 57 N2 patients eligible for the study, 28 for immunotherapy and 29 for chemotherapy. For the 28 immunotherapy cases, a total of 313 courses of immunotherapy were administered. The main toxicities were fever (78.0%), chill (83.4%). The 5-year survival rates in the immunotherapy and chemotherapy groups were 56.5% and 12.5% respectively. Among the variables analyzed, immunotherapy was the most significant independent prognostic factor (p=0.0042.) Conclusions: Adoptive transfer of activated killer cells and dendritic cells from the tumor draining lymph nodes of primary lung cancer patients is safe and feasible, and a large-scale multi-institutional study is necessary for the evaluation of the efficacy of this treatment. No significant financial relationships to disclose.

Serum level of vascular endothelial growth factor (VEGF) as an independent prognostic factor in metastatic renal cell carcinoma (MRCC)

5044 Background: The French Immunotherapy Group previously showed that circulating interleukin-6 (IL-6) and VEGF correlate with survival in MRCC patients (pts) (Négrier JCO 2004). We aimed to confirm the prognostic value of IL-6 and VEGF, and to test that of macrophage colony-stimulating factor (M-CSF) and macrophage inflammatory protein 3-alpha (MIP-3a) for survival in MRCC pts of good and intermediate prognoses. Patients and Methods: Pre-treatment samples were obtained from 302 MRCC pts enrolled in 2 parallel multicenter randomized cytokine trials. Baseline serum levels of IL-6, M-CSF, VEGF, and MIP3a were determined by immunoassays; their prognostic value for progression-free survival (PFS) and overall survival (OS) was tested. Characteristics of pts with a 0.15 significance level in univariate analysis (ECOG PS, prior therapy, metastatic sites and biological parameters) were entered in a multivariate Cox model. A backward stepwise procedure discriminated non-influential variables at 0.05 level. Results: Median IL6, VEGF, M-CSF and MIP3a levels were respectively 7.3 (range 0–392 pg/mL), 0.5 (0–2.3 ng/mL), 406 (0–4,785 pg/mL) and 0 (0–1,705 ng/mL). IL6 or M-CSF and VEGF (p&lt;0.0001), or IL6 and M-CSF (p=0.0005) were significantly correlated. Death occurred in 192/302 pts, with 20.9 month median OS. OS was highly correlated with IL6, VEGF and M-CSF (p &lt;0.001) but not with MIP3a (p=0.06) in univariate analysis. Only VEGF remained independently prognostic for OS in multivariate analysis (39% increased probability of death if VEGF level doubled) after adjustment on PS, time from diagnosis to metastasis, number of metastatic sites, pleural metastasis, abnormal sedimentation rate, haemoglobin and LDH levels. Similar results were found for PFS, with a hazard ratio of 1.19 for a 2-fold VEGF increase. Conclusions: The independent prognostic value of serum IL6 level is not confirmed in our cohort that excluded pts with poor outcome, but serum VEGF level appears as an independent prognostic factor, thus supporting the therapeutic interest for these pts of newly available drugs targeting VEGF receptors. No significant financial relationships to disclose.

Specific immunotherapy is effective in the prevention of new sensitivities

Background Allergen specific immunotherapy is the only specific and curative approach in the treatment of IgE-mediated allergic diseases such as bronchial asthma and allergic rhinitis. The safety and clinical efficacy of this treatment are well documented but data on the prevention of new sensitizations remain scarce. Objective To demonstrate the efficacy of specific immunotherapy in allergic respiratory diseases in childhood and to determine whether this treatment prevents the development of new sensitizations in children sensitized to house dust mite or pollen species. Methods Fifty-six patients received specific immunotherapy (43 sensitive to house dust mite and 13 sensitive to pollen). Fifty-one patients not receiving immunotherapy but treated with pharmacotherapy were enrolled in the control group. The patients were followed-up for at least 4 years and treatment efficacy and the development of new sensitizations were compared between the two groups. Results The number of patients with symptoms was significantly decreased in both groups at the end of the treatment period. No new sensitizations were found in 35 of the 43 (81.39 %) patients in the house dust mite immunotherapy group and in 10 of 13 (76.92 %) patients in the pollen immunotherapy group. In contrast, 20 of 51 (39.21 %) patients in the control group showed new sensitizations. The difference between the house dust mite and pollen immunotherapy groups and the control group in this parameter was statistically significant (p = 0.033). Conclusion Our data demonstrate that administration of specific immunotherapy in allergic patients significantly reduced symptoms and the development of new sensitivities.

Allergen injection immunotherapy for seasonal allergic rhinitis

Allergic rhinitis is the most common of the allergic diseases. Despite improved understanding of the pathophysiology of allergic rhinitis and advances in its pharmacological treatment, its prevalence has increased worldwide. For patients whose symptoms remain uncontrolled despite medical treatment, allergen injection immunotherapy is advised. An allergen-based treatment may reduce symptoms, the need for medication and modify the natural course of this disease. To evaluate the efficacy and safety of subcutaneous specific allergen immunotherapy, compared with placebo, for reducing symptoms and medication requirements in seasonal allergic rhinitis patients. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), Pre-MEDLINE, KOREAMED, INDMED, LILACS, PAKMEDINET, Scisearch, mRCT and the National Research Register. The date of the last search was February 2006. All studies identified by the searches were assessed to identify randomised controlled trials involving participants with symptoms of seasonal allergic rhinitis and proven allergen sensitivity, treated with subcutaneous allergen specific immunotherapy or corresponding placebo. Two independent authors identified all studies reporting double-blind, placebo controlled randomised trials of specific immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Two authors independently performed quality assessment of studies. Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.2.8. Analysis was performed using the Standardised Mean Difference (SMD) method and a random-effects model; P values < 0.05 were considered statistically significant. The primary outcome measures were symptom scores, medication use, quality of life and adverse events. We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In total there were 2871 participants (1645 active, 1226 placebo), each receiving on average 18 injections. Duration of immunotherapy varied from three days to three years. Symptom score data from 15 trials were suitable for meta-analysis and showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97 to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33, p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14085 injections) of those on active treatment and in 0.01% (1 of 8278 injections) of the placebo group for treatment of adverse events. There were no fatalities. This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events.

Adoptive Transfer of Splenocytes from Immunotherapy Group Ameliorating the Histopathological Changes and Increased IL-10 and IFN-g Levels in the Recipient Mice

RATIONALE: In this study we tested whether adoptive transfer of splenocytes of mice that received intranasal ovalbumin(OVA)-immunotherapy to naive recipient mice prior to the establishment of asthma model was successful in ameliorating airway histopathology in recipients.

Ribosomal therapy in the prophylaxis of recurrent pharyngotonsillitis in children

Although much has been written on how to manage recurrent pharyngotonsillitis, it remains a controversial topic. The composition of normal commensal oropharynx bacteria may be disrupted by frequently using antimicrobials, by inhibiting sensitive organisms and by allowing resistant organisms to overgrowth. This may cause the recurrence of acute episodes. The aim of this study was to evaluate the efficacy of ribosomal immunotherapy in the prophylaxis of recurrent pharyngotonsillitis. A total of 160 children aged between 5 and 14 years with recurrent pharyngotonsillitis were ramdomized to receive either ribosomal immunotherapy (group A one tablet a day, 8 days a month for 3 months) or a placebo (group B same dosage for the same period). At the end of the study, each patient treated with Immucytal presented a subjective decrease of symptoms. Compared with group B, group A experienced a significant improvement of some clinical parameters. The results show that ribosomal immunotherapy causes a significant improvement of both specific and non-specific immunity and may be effective in the prophylaxis of recurrent pharyngotonsillitis and in preventing recurrences without entailing side effects or bacterial resistance.

Sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma

The objective of the current study was to determine the significance of sarcomatoid differentiation as a prognostic factor for immunotherapy in metastatic renal cell carcinoma (RCC). Patients with metastatic RCC were included in this study and were categorized according to sarcomatoid differentiation. Patients with sarcomatoid differentiation had more aggressive tumor characteristics than those without sarcomatoid differentiation. After immunotherapy, the median progression-free survival was 9.0 months (95% confidence interval [CI] 1.4-52.7) for patient without sarcomatoid differentiation and 3.2 months (95% CI 0.4-42.9) for patients with sarcomatoid differentiation, respectively (P=0.0001). The median overall survival was 22.2 months (95% CI 3.2-75.4) and 10.0 months (95% CI 0.7-60.1) in both groups. When comparing patients with sarcomatoid differentiation, there was no significant difference of overall survival in the immunotherapy group and the no immunotherapy group. Multivariate Cox proportional hazards model analysis showed that T stage (Hazard ratio [HR] 1.71; 95% CI 1.07-2.74; P=0.024), sarcomatoid differentiation (HR 2.18; 95% CI 1.30-3.66; P = 0.003), and the number of metastasis sites (HR 1.81; 95% CI 1.14-2.88; P=0.012) were independent predictors of progression-free survival. Sarcomatoid differentiation and the number of metastasis sites were independent prognostic predictors of overall survival. The estimated relative risks of sarcomatoid differentiation and the number of metastasis sites were 2.83 (95% CI 1.49-5.40; P=0.002) and 2.31 (95% CI 1.29-4.16; P=0.005), respectively. Our findings suggest that sarcomatoid differentiation is an important prognostic factor for immunotherapy in metastatic RCC.