INJECTABLE 3 -D VACCINES COULD FIGHT CANCER, INFECTIOUS DISEASES
One of the reasons cancer is so deadly is that it can evade attack from
the body's immune system, which allows tumors to flourish and spread.
Scientists can try to induce the immune system, known as immunotherapy, to go
into attack mode to fight cancer and to build long lasting immune resistance to
cancer cells. Now, researchers at the Wyss Institute for Biologically Inspired
Engineering at Harvard University and Harvard's School of Engineering and
Applied Sciences (SEAS) show a non-surgical injection of programmable
biomaterial that spontaneously assemblesin vivo into a 3D structure could fight and
even help prevent cancer and also infectious disease such as HIV. Their
findings are reported in Nature Biotechnology
"We can create 3D
structures using minimally-invasive delivery to enrich and activate a host's
immune cells to target and attack harmful cells in vivo," said
the study's senior author David Mooney, Ph.D., who is a Wyss Institute Core
Faculty member and the Robert P. Pinkas Professor of Bioengineering at Harvard
SEAS.
Tiny biodegradable
rod-like structures made from silica, known as mesoporous silica rods (MSRs),
can be loaded with biological and chemical drug components and then delivered
by needle just underneath the skin. The rods spontaneously assemble at the vaccination
site to form a three-dimensional scaffold, like pouring a box of matchsticks
into a pile on a table. The porous spaces in the stack of MSRs are large enough
to recruit and fill up with dendritic cells, which are "surveillance"
cells that monitor the body and trigger an immune response when a harmful
presence is detected.
"Nano-sized
mesoporous silica particles have already been established as useful for
manipulating individual cells from the inside, but this is the first time that
larger particles, in the micron-sized range, are used to create a 3D in
vivo scaffold that can recruit and attract tens of millions of immune
cells," said co-lead author Jaeyun Kim, Ph.D., an Assistant Professor of
Chemical Engineering at Sungkyunkwan University and a former Wyss Institute
Postdoctoral Fellow.
Synthesized in the
lab, the MSRs are built with small holes, known as nanopores, inside. The
nanopores can be filled with specific cytokines, oligonucleotides, large
protein antigens, or any variety of drugs of interest to allow a vast number of
possible combinations to treat a range of infections.
"Although right
now we are focusing on developing a cancer vaccine, in the future we could be
able to manipulate which type of dendritic cells or other types of immune cells
are recruited to the 3D scaffold by using different kinds of cytokines released
from the MSRs," said co-lead author Aileen Li, a graduate student pursuing
her Ph.D. in bioengineering at Harvard SEAS. "By tuning the surface
properties and pore size of the MSRs, and therefore controlling the
introduction and release of various proteins and drugs, we can manipulate the
immune system to treat multiple diseases."
Once the 3D scaffold
has recruited dendritic cells from the body, the drugs contained in the MSRs
are released, which trips their "surveillance" trigger and initiates
an immune response. The activated dendritic cells leave the scaffold and travel
to the lymph nodes, where they raise alarm and direct the body's immune system
to attack specific cells, such as cancerous cells. At the site of the
injection, the MSRs biodegrade and dissolve naturally within a few months.
So far, the
researchers have only tested the 3D vaccine in mice, but have found that it is
highly effective. An experiment showed that the injectable 3D scaffold
recruited and attracted millions of dendritic cells in a host mouse, before
dispersing the cells to the lymph nodes and triggering a powerful immune
response.
The vaccines are
easily and rapidly manufactured so that they could potentially be widely
available very quickly in the face of an emerging infectious disease. "We
anticipate 3D vaccines could be broadly useful for many settings, and their
injectable nature would also make them easy to administer both inside and
outside a clinic," said Mooney.
Since the vaccine
works by triggering an immune response, the method could even be used
preventatively by building the body's immune resistance prior to infection.
"Injectable
immunotherapies that use programmable biomaterials as a powerful vehicle to
deliver targeted treatment and preventative care could help fight a whole range
of deadly infections, including common worldwide killers like HIV and Ebola, as
well as cancer," said Wyss Institute Founding Director Donald Ingber,
M.D., Ph.D. who is alsoJudah Folkman Professor of Vascular Biology at
Harvard Medical School and Boston Children's Hospital, and Professor of
Bioengineering at Harvard SEAS. "These injectable 3D vaccines offer a
minimally invasive and scalable way to deliver therapies that work by mimicking
the body's own powerful immune-response in diseases that have previously been
able to skirt immune detection."
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