64 research outputs found
Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma
Background Equine melanoma has a high incidence in grey horses. Xenogenic DNA
vaccination may represent a promising therapeutic approach against equine
melanoma as it successfully induced an immunological response in other species
suffering from melanoma and in healthy horses. In a clinical study, twenty-
seven, grey, melanoma-bearing, horses were assigned to three groups (nâ=â9)
and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq)
IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp)
100 or human tyrosinase (htyr). Horses were vaccinated intramuscularly, and
one selected melanoma was locally treated by intradermal peritumoral
injection. Prior to each injection and on day 120, the sizes of up to nine
melanoma lesions per horse were measured by caliper and ultrasound. Specific
serum antibodies against hgp100 and htyr were measured using cell based flow-
cytometric assays. An Analysis of Variance (ANOVA) for repeated measurements
was performed to identify statistically significant influences on the relative
tumor volume. For post-hoc testing a Tukey-Kramer Multiple-Comparison Test was
performed to compare the relative volumes on the different examination days.
An ANOVA for repeated measurements was performed to analyse changes in body
temperature over time. A one-way ANOVA was used to evaluate differences in
body temperature between the groups. A pâvalueâ<â0.05 was considered
significant for all statistical tests applied. Results In all groups, the
relative tumor volume decreased significantly to 79.1â±â26.91% by day 120 (pâ<
0.0001, Tukey-Kramer Multiple-Comparison Test). Affiliation to treatment
group, local treatment and examination modality had no significant influence
on the results (ANOVA for repeated measurements). Neither a cellular nor a
humoral immune response directed against htyr or hgp100 was detected. Horses
had an increased body temperature on the day after vaccination. Conclusions
This is the first clinical report on a systemic effect against equine melanoma
following treatment with DNA vectors encoding eqIL12 and eqIL18 and formulated
with a transfection reagent. Addition of DNA vectors encoding hgp100
respectively htyr did not potentiate this effect
The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network
Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers.
Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientĆ delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment.
Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects
Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent
Background Deoxyribonucleic acid (DNA) vaccines are used for experimental
immunotherapy of equine melanoma. The injection of complexed linear DNA
encoding interleukin (IL)-12/IL-18 induced partial tumour remission in a
clinical study including 27 grey horses. To date, the detailed mechanism of
the anti-tumour effect of this treatment is unknown. Results In the present
study, the clinical and cellular responses of 24 healthy horses were monitored
over 72 h after simultaneous intradermal and intramuscular application of
equine IL-12/IL-18 DNA (complexed with a transfection reagent) or comparative
substances (transfection reagent only, nonsense DNA, nonsense DNA depleted of
CG). Although the strongest effect was observed in horses treated with
expressing DNA, horses in all groups treated with DNA showed systemic
responses. In these horses treated with DNA, rectal temperatures were elevated
after treatment and serum amyloid A increased. Total leukocyte and neutrophil
counts increased, while lymphocyte numbers decreased. The secretion of tumour
necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from peripheral
mononuclear blood cells ex vivo increased after treatments with DNA, while
IL-10 secretion decreased. Horses treated with DNA had significantly higher
myeloid cell numbers and chemokine (C-X-C motif) ligand (CXCL)-10 expression
in skin samples at the intradermal injection sites compared to horses treated
with transfection reagent only, suggesting an inflammatory response to DNA
treatment. In horses treated with expressing DNA, however, local CXCL-10
expression was highest and immunohistochemistry revealed more intradermal
IL-12-positive cells when compared to the other treatment groups. In contrast
to non-grey horses, grey horses showed fewer effects of DNA treatments on
blood lymphocyte counts, TNFα secretion and myeloid cell infiltration in the
dermis. Conclusion Treatment with complexed linear DNA constructs induced an
inflammatory response independent of the coding sequence and of CG motif
content. Expressing IL-12/IL-18 DNA locally induces expression of the
downstream mediator CXCL-10. The grey horses included appeared to display an
attenuated immune response to DNA treatment, although grey horses bearing
melanoma responded to this treatment with moderate tumour remission in a
preceding study. Whether the different immunological reactivity compared to
other horses may contributes to the melanoma susceptibility of grey horses
remains to be elucidated
Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent
Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California
Abstract Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level
In vitro evidence of efficacy and safety of a polymerized cat dander extract for allergen immunotherapy
An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1, the major cat allergen
Background: Cats are the major source of indoor inhalant allergens after house dust mites. The global incidence of cat allergies is rising sharply, posing a major public health problem. Ten cat allergens have been identified. The major allergen responsible for symptoms is Fel d 1, a secretoglobin and not a lipocalin, making the cat a special case among mammals.
Main body: Given its clinical predominance, it is essential to have a good knowledge of this allergenic fraction, including its basic structure, to understand the new exciting diagnostic and therapeutic applications currently in development. The recent arrival of the component-resolved diagnosis, which uses molecular allergens, represents a unique opportunity to improve our understanding of the disease. Recombinant Fel d 1 is now available for in vitro diagnosis by the anti-Fel d 1 specific IgE assay. The first part of the review will seek to describe the recent advances related to Fel d 1 in terms of positive diagnosis and assessment of disease severity. In daily practice, anti-Fel d 1 IgE tend to replace those directed against the overall extract but is this attitude justified? We will look at the most recent arguments to try to answer this question. In parallel, a second revolution is taking place thanks to molecular engineering, which has allowed the development of various forms of recombinant Fel d 1 and which seeks to modify the immunomodulatory properties of the molecule and thus the clinical history of the disease via various modalities of anti-Fel d 1-specific immunotherapy. We will endeavor to give a clear and practical overview of all these trends
Ambrosia artemisiifolia (ragweed) in Germany â current presence, allergological relevance and containment procedures
The Impact of Sex and Age on the Prevalence of Clinically Relevant Sensitization and Asymptomatic Sensitization in the General Population
Types of Artemisia pollen season depending on the weather conditions in WrocĆaw (Poland), 2002â2011
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