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mouse. Successful transgene expression was observed in 2 days, which peaked at
day 7 and persisted until day 14. The cells multiplied were endothelial cells, with a
significant amount of VEGF secreted in the conditioned media of cells
[48]
.
Plasmid DNA vaccination combined with EP provides a promising approach for
the prevention of infectious diseases and for cancer immunotherapy. Several reports
showed EP has adjuvant-like properties when combined with plasmid DNA injec-
tion, although the effect in the absence of DNA was not investigated. Mouse skeletal
muscle after EP only showed recruitment and triggering of cells involved in antigen
presentation and immune response, hence indicating that EP has adjuvant-like prop-
erties, probably because of moderate tissue injury and the generation of a proinflam-
matory context with cytokine release that enhances the immune response
[49]
.
The
in vivo
EP was utilized to enhance plasmid DNA expression in sheep muscle
to improve the immune response to
Haemonchus contortus
antigen DNA vaccina-
tion, with minimal muscle damage and enhanced humoral responses in electropor-
ated sheep
[50]
. It is generally recognized that DNA vaccines are often less effective
in large animals than in mice. One possible reason for this reduced effectiveness may
be transfection efficiency and the low level of expression elicited by plasmid vectors
in large animals. Enhanced efficiency of DNA vaccination after EP in large animals
such as pigs, using EP and plasmids encoding two different genes (bovine herpes
virus glycoprotein D [gD] and hepatitis B surface antigen [HBsAg] and two different
electrodes [a single-needle electrode and a six-needle electrode]) has shown signifi-
cant immunization
[51]
. A DNA prime/protein boost strategy to examine the effect of
DNA priming with EP on the immune response after a protein boost was also studied
for enhanced immune response using EP
[51]
.
The key to success with nonviral gene therapy as a treatment for cancer is to dis-
cover effective therapeutic genes and gene delivery methods and to understand how
tumors are eradicated. EP has also been widely used in gene therapy for cancer treat-
ment, and EP of IFN- DNA into tumors in SCCVII tumor-bearing mice demon-
strated tumor eradication in 50% of the mice and a more than twofold increase in
survival time when compared with controls
[52]
. Furthermore, administration of
10 g of IFN-alpha DNA plasmid once a week for 3 weeks increased INF-alpha
expression in muscle and serum, with increased survival time and reduced squamous
cell carcinoma (SCC) growth at a distant site in the C3H/HeJ-immunocompetent
mouse. As well, it increased expression levels of the antiangiogenic genes IP-10 and
Mig in local tumor tissue, which leads to a reduction of blood vessels observed at
the local tumor site, thus increasing the survival rate of animals
[53]
. The EP of
IL-
12
gene for hepatocellular carcinoma (HCC) was also investigated with optimized
conditions of electric pulses (voltage, pulsing duration, numbers of shocks) in subcu-
taneously implanted MH134 cells to C3H mice for HCC establishment. Intratumoral
administration of the
IL-12
vector elevated serum
IL-12
and IFN- also significantly
inhibited the growth of HCC into which the
mIL-12
vector had been directly trans-
ferred, and also of the distant HCC. These results demonstrate that gene therapy for
HCC using EP
in vivo
using
IL-12
is very efficient and is thus promising for fur-
ther clinical trial
[54]
. EP along with sonophoresis, or electrosonoporation, was also
employed for muscle-targeted
IL-12
gene therapy of orthotopic HCC with significant
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