- A research team from Wistar Institute has developed
a DNA vaccine which was found to increase the immune response of the host
- The altered sequences of DNA found in the vaccine
marked the cancer antigen as foreign
- The increased immune response aided in better
therapy for cancer with no side effects
A research team fromThe Wistar Institute and Inovio Pharmaceuticals Inc. has
developed a DNA vaccine using molecular techniques that increased the immune
response against important cancer antigen targets. This study, published in the
Journal of Molecular therapy
, could improve cancer immunotherapy
by harnessing the body's
natural defense systems.
There are two types of antigens
that are carried by cancer cells, self-antigens as well as cancer associated
antigens. The presence of these cancer associated antigens enable the cancer
cells to be recognized as foreign by the body's immune system, mounting an
attack by T cells. The antigens that are expressed by the cancer cells are
are expressed in large numbers by cancer cells
than in normal cells, which results them in
being viewed as foreign.
which are not expressed by the cells in a tissue are regarded as
foreign by the immune system.
- Antigens that are expressed as a result of gene
mutations that give risk to cancer and which have not been previously seen
by the immune system.
The main reason for the inability
of the immune system to mount an immune response against cancer is because
cancer associated antigens are only marginally altered versions of the
self-antigens, which results in a weak immune response.
Genetic Changes in Cancer Cells
There are genetics changes in
cancer cells that result in the loss of cancer associated antigens. This
results in the evasion of the host's immune system. The growing cancer may be
perceived as a threat by the immune system but it may still escape a strong
immune attack from the host.
DNA Vaccines-Cancer Immunotherapy
The cancer immunotherapy
strategies are aimed at utilizing the natural immune defenses of the host in
identifying cancer cells and killing them. DNA vaccines are administered
intramuscularly and include a sequence of synthetically designed DNA, which
contain information that can be used to activate the host immune system.
Previous studies have shown that
the use of these DNA vaccines can be used to generate a strong immune response
against tumors that are caused by viral infection as well as for infectious
diseases. The DNA vaccines are used to target the tumor-associated
antigens as well as proteins which are
exclusively expressed by tumor cells but not by normal
Vaccines that have been designed
for solely targeting the tumor associated antigens have not been able to produce
considerable therapeutic effects. This is because of poor immunogenicity of the
vaccines as the antigens expressed by the cancer cells are recognized as
self-antigens. This immune tolerance by the immune system prevents autoimmunity
which limits the effectiveness of the DNA vaccine.
Wilm's Tumor Gene 1 (WT1)
In Wilm's tumor
gene 1 (WT1), an overexpression of the tumor antigen plays
a crucial role in the development of a tumor. Vaccines that have been developed
against WT1 have not been effective thus far due to poor immune responses
mediated by immune tolerance. In the current study, the
research team from Wistar developed a DNA vaccine that
used modified sequences of DNA which mark the WT1 as foreign
to the immune system of the host, leading dissolution of the immune tolerance.
‘DNA vaccines with altered DNA sequences will aid in breaking immune tolerance of the host’
President and the Director of the Vaccine Center
(Wistar Institute) Dr. David B. Weiner,
who is also the W.W. Smith Charitable Trust Professor in
Cancer Research said that this is an important step in the development
of therapy for cancer.
This senior author of the study,
further stated that the immune responses provided a unique tool that could be
used to treat patients with different types of cancer. This vaccine could be
combined with other immune approaches like checkpoint inhibitors, which
increases immune therapy against certain cancers.
The DNA vaccine that has been
developed by the research team from Weiner Institute
was optimized using a synthetic DNA sequence for WT1,
- DNA sequences that had high
homology with the native sequence
- New altered DNA sequences which differed from native WT1 to make them recognizable by the immune system of the host.
The novel vaccine that was
designed by these scientists induced WT1-specific, T cell responses
along with production of antibodies, but there were no side effects that
were caused in both mice as well as in non-human primates. This vaccine was
found to be superior to the other traditional vaccines that are available as
they were able to break the immune tolerance and result in long-term immune
response. There was therapeutic stimulation of anti-tumor response in mice.
The multiple benefits associated
with DNA vaccines makes them ideal for use in patients suffering from different
types of cancer. Further research that details effectiveness in humans could
soon provide insights into its potential use as
- Cancer Vaccines - (https://www.cancer.gov/about-cancer/causes-prevention/vaccines-fact-sheet)