Abstract
Background
Despite
advancements
in
the
successful
use
of
immunotherapy
treating
a
variety
solid
tumors,
applications
brain
tumors
have
lagged
considerably.
This
is
due,
at
least
part,
to
lack
well-characterized
antigens
expressed
within
that
can
mediate
tumor
rejection;
low
mutational
burden
these
limits
abundance
targetable
neoantigens;
and
immunologically
“cold”
microenvironment
hampers
generation
sustained
productive
immunologic
responses.
The
field
mRNA-based
therapeutics
has
experienced
boon
following
universal
approval
COVID-19
mRNA
vaccines.
immunotherapeutics
also
garnered
widespread
interest
for
their
potential
revolutionize
cancer
treatment.
In
this
study,
we
developed
novel
scalable
approach
production
personalized
target
multiple
rejection
single
therapy
treatment
refractory
tumors.
Methods
Tumor-specific
neoantigens
aberrantly
overexpressed
tumor-associated
were
identified
glioblastoma
medulloblastoma
using
our
immunogenomics
pipeline
called
O
pen
R
eading
Frame
A
ntigen
N
etwork
(O.R.A.N).
Personalized
antigen-specific
vaccine
was
each
individual
model
selective
gene
capture
enrichment
strategy.
immunogenicity
efficacy
vaccines
evaluated
combination
with
anti-PD-1
immune
checkpoint
blockade
or
adoptive
cellular
ex
vivo
expanded
lymphocytes
highly
aggressive
murine
GBM
models.
Results
Our
results
demonstrate
effectiveness
eliciting
robust
anti-tumor
responses
hosts.
findings
substantiate
an
increase
tumor-infiltrating
characterized
by
enhanced
effector
function,
both
intratumorally
systemically,
after
mRNA-directed
immunotherapy,
resulting
favorable
shift
from
cold
hot.
Capacity
generate
targeting
human
demonstrated.
Conclusions
We
established
customizable
mRNA-therapeutic
effectively
targets
plurality
demonstrated
potent
response
preclinical
platform
technology
uniquely
addresses
challenge
heterogeneity
antigen
burden,
two
key
deficiencies
classically
immunotherapy-resistant
CNS
malignancies,
possibly
other
types.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Июль 19, 2023
Abstract
Adjuvants
are
indispensable
components
of
vaccines.
Despite
being
widely
used
in
vaccines,
their
action
mechanisms
not
yet
clear.
With
a
greater
understanding
the
by
which
innate
immune
response
controls
antigen-specific
response,
adjuvants’
beginning
to
be
elucidated.
can
categorized
as
immunostimulants
and
delivery
systems.
Immunostimulants
danger
signal
molecules
that
lead
maturation
activation
antigen-presenting
cells
(APCs)
targeting
Toll-like
receptors
(TLRs)
other
pattern
recognition
(PRRs)
promote
production
antigen
signals
co-stimulatory
signals,
turn
enhance
adaptive
responses.
On
hand,
systems
carrier
materials
facilitate
presentation
prolonging
bioavailability
loaded
antigens,
well
antigens
lymph
nodes
or
APCs.
The
systematically
summarized
at
this
review.
This
is
followed
an
introduction
mechanisms,
properties,
progress
classical
vaccine
adjuvants.
Furthermore,
since
some
adjuvants
under
investigation
exhibit
potency
than
adjuvants,
could
compensate
for
deficiencies
summary
adjuvant
platforms
subsequently
presented.
Notably,
we
highlight
different
immunological
properties
these
platforms,
will
provide
wide
range
options
rational
design
basis,
review
points
out
development
prospects
problems
should
paid
attention
future.
Advanced Materials,
Год журнала:
2023,
Номер
35(51)
Опубликована: Май 17, 2023
Abstract
Messenger
RNA
(mRNA)
has
received
great
attention
in
the
prevention
and
treatment
of
various
diseases
due
to
success
coronavirus
disease
2019
(COVID‐19)
mRNA
vaccines
(Comirnaty
Spikevax).
To
meet
therapeutic
purpose,
it
is
required
that
must
enter
target
cells
express
sufficient
proteins.
Therefore,
development
effective
delivery
systems
necessary
crucial.
Lipid
nanoparticle
(LNP)
represents
a
remarkable
vehicle
indeed
accelerated
applications
humans,
as
several
mRNA‐based
therapies
have
already
been
approved
or
are
clinical
trials.
In
this
review,
focus
on
mRNA‐LNP‐mediated
anticancer
therapy.
It
summarizes
main
strategies
mRNA‐LNP
formulations,
discusses
representative
approaches
cancer,
points
out
current
challenges
possible
future
directions
research
field.
hoped
these
delivered
messages
can
help
further
improve
application
technology
cancer
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 24, 2023
Immunotherapy
has
ushered
in
a
new
era
cancer
treatment,
and
immunotherapy
continues
to
be
rejuvenated.
The
clinical
goal
of
is
prime
host
immune
system
provide
passive
or
active
immunity
against
malignant
tumors.
Tumor
infiltrating
leukocytes
(TILs)
play
an
immunomodulatory
role
tumor
microenvironment
(TME)
which
closely
related
escape
cells,
thus
influence
progress.
Several
immunotherapies,
include
checkpoint
inhibitors
(ICIs),
vaccine,
adoptive
cell
transfer
(ACT),
have
shown
great
efficacy
promise.
In
this
review,
we
will
summarize
the
recent
research
advances
immunotherapy,
including
molecular
mechanisms
effects
as
well
limitations
immunotherapy.
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(11)
Опубликована: Март 4, 2024
Lipid
nanoparticles
(LNPs)
have
recently
emerged
as
a
powerful
and
versatile
clinically
approved
platform
for
nucleic
acid
delivery,
specifically
mRNA
vaccines.
A
major
bottleneck
in
the
field
is
release
of
mRNA-LNPs
from
endosomal
pathways
into
cytosol
cells
where
they
can
execute
their
encoded
functions.
The
data
regarding
mechanism
these
escape
processes
are
limited
contradicting.
Despite
extensive
research,
there
no
consensus
compartment
escape,
cause
inefficient
currently
lacking
robust
method
to
detect
escape.
Here,
we
review
known
mechanisms
available
methods
study
this
process.
We
critically
discuss
limitations
challenges
possibilities
overcome
challenges.
propose
that
development
robust,
quantitative
high-throughput
techniques
timely
essential.
better
understanding
process
will
enable
RNA-LNP
designs
with
improved
efficiency
unlock
new
therapeutic
modalities.
Clinical and Translational Medicine,
Год журнала:
2023,
Номер
13(8)
Опубликована: Авг. 1, 2023
Abstract
Messenger
ribonucleic
acid
(mRNA)
vaccines
are
a
relatively
new
class
of
that
have
shown
great
promise
in
the
immunotherapy
wide
variety
infectious
diseases
and
cancer.
In
past
2
years,
SARS‐CoV‐2
mRNA
contributed
tremendously
against
SARS‐CoV2,
which
has
prompted
arrival
vaccine
research
boom,
especially
cancer
vaccines.
Compared
with
conventional
vaccines,
significant
advantages,
including
efficient
production
protective
immune
responses,
low
side
effects
lower
cost
acquisition.
this
review,
we
elaborated
on
development
as
well
potential
biological
mechanisms
latest
progress
various
tumour
treatments,
discussed
challenges
future
directions
for
field.
Pharmaceutics,
Год журнала:
2023,
Номер
15(7), С. 1972 - 1972
Опубликована: Июль 18, 2023
Messenger
RNA
(mRNA)
vaccine
development
for
preventive
and
therapeutic
applications
has
evolved
rapidly
over
the
last
decade.
The
mRVNA
proven
efficacy
in
various
applications,
including
infectious
disease,
immunotherapy,
genetic
disorders,
regenerative
medicine,
cancer.
Many
mRNA
vaccines
have
made
it
to
clinical
trials,
a
couple
obtained
FDA
approval.
This
emerging
approach
several
advantages
conventional
methods:
safety;
efficacy;
adaptability;
bulk
production;
cost-effectiveness.
However,
is
worth
mentioning
that
delivery
target
site
vivo
degradation
thermal
stability
are
boundaries
can
alter
their
outcomes.
In
this
review,
we
shed
light
on
different
types
of
vaccines,
mode
action,
process
optimize
overcome
limitations.
We
also
explored
systems
focusing
nanoparticle-mediated
vaccine.
Generally,
system
plays
vital
role
enhancing
stability,
biocompatibility,
homing
desired
cells
tissues.
addition
function
as
vehicle,
they
serve
compartment
shields
protects
molecules
against
physical,
chemical,
biological
activities
efficiency.
Finally,
focused
future
considerations
should
be
attained
safer
more
efficient
application
underlining
disadvantages
current
vaccines.
