11 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 (n = 9)
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 p–value < 0.05 was considered
significant for all statistical tests applied. Results In all groups, the
relative tumor volume decreased significantly to 79.1 ± 26.91% by day 120 (p <
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
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
From Complicit Citizens to Potential Prey: State Imaginaries and Subjectivities in US War Resistance
The movements against the Vietnam and Iraq wars gave rise to analogous resistance efforts, in the form of draft resistance and counter-recruitment, respectively. Despite their many similarities, the draft resistance and counter-recruitment movements emerged in distinct historical eras marked by very different ‘state imaginaries’ or assumptions about the nature of the state and people’s relation to it. Drawing on original archival work, this paper excavates these state imaginaries and examines how they conditioned activists’ subjectivities in each era. More specifically, this paper argues that the 1960s were marked by an imaginary of the state based on consent, which positioned draft resisters as complicit citizens and engendered a sense of personal responsibility for the war. This state imaginary was displaced in the neoliberal era by an imaginary of the state as an alien and invasive force, which positioned counter-recruitment activists (or their children) as potential prey and impelled efforts at self-defense