Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 20, 2025
Abstract
mRNA
therapy
is
a
promising
approach
in
oncology,
offering
innovative
applications
such
as
tumor
vaccines,
protein
replacement
therapy,
cell
and
gene
therapy.
However,
challenges
stability
delivery
efficiency
must
be
addressed.
Advances
system
technologies
are
crucial
for
precise
delivery,
enhancing
treatment
safety
efficacy.
The
development
of
systems
requires
accurate
organ
or
targeting,
intelligent
release
mechanisms,
optimized
administration
routes.
This
review
outlines
the
well
utilization
nonviral
vectors,
encompassing
organic,
inorganic,
biomimetic
systems.
It
further
elucidates
strategies
passive
active
vector
targeting
examines
recent
advances
realm
stimuli‐responsive
that
sensitive
to
pH
ultrasound.
Additionally,
addresses
noninvasive
designed
oral
pulmonary
administration.
current
emerging
trends
discussed,
potential
mitigate
these
issues
emphasized.
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Окт. 3, 2024
Chimeric
Antigen
Receptor
(CAR)
technology
has
revolutionized
cellular
immunotherapy,
particularly
with
the
success
of
CAR-T
cells
in
treating
hematologic
malignancies.
However,
have
limited
efficacy
against
solid
tumors.
To
address
these
limitations,
CAR-macrophages
(CAR-Ms)
leverage
innate
properties
macrophages
specificity
and
potency
CAR
technology,
offering
a
novel
promising
approach
to
cancer
immunotherapy.
Preclinical
studies
shown
that
CAR-Ms
can
effectively
target
destroy
tumor
cells,
even
within
challenging
microenvironments,
by
exhibiting
direct
cytotoxicity
enhancing
recruitment
activation
other
immune
cells.
Additionally,
favorable
safety
profile
their
persistence
tumors
position
as
potentially
safer
more
durable
therapeutic
options
compared
This
review
explores
recent
advancements
including
engineering
strategies
optimize
anti-tumor
preclinical
evidence
supporting
use.
We
also
discuss
challenges
future
directions
developing
therapies,
emphasizing
potential
revolutionize
By
harnessing
unique
macrophages,
offer
groundbreaking
overcoming
current
limitations
cell
paving
way
for
effective
sustainable
treatments.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Ноя. 28, 2023
Macrophages
and
neutrophils
are
the
main
components
of
innate
immune
system
play
important
roles
in
promoting
angiogenesis,
extracellular
matrix
remodeling,
cancer
cell
proliferation,
metastasis
tumor
microenvironment
(TME).
They
can
also
be
harnessed
to
mediate
cytotoxic
killing
effects
orchestrate
effective
anti-tumor
responses
with
proper
stimulation
modification.
Therefore,
macrophages
have
strong
potential
immunotherapy.
In
this
review,
we
briefly
outlined
applications
or
adoptive
therapies,
focused
on
chimeric
antigen
receptor
(CAR)-engineered
(CAR-Ms)
(CAR-Ns).
We
summarized
construction
strategies,
preclinical
clinical
studies
CAR-Ms
CAR-Ns.
end,
discussed
limitations
challenges
CAR-Ns,
as
well
future
research
directions
extend
their
treating
solid
tumors.
Cellular and Molecular Immunology,
Год журнала:
2024,
Номер
21(11), С. 1335 - 1349
Опубликована: Окт. 8, 2024
The
potential
of
macrophage-mediated
phagocytosis
as
a
cancer
treatment
is
promising.
Blocking
the
CD47-SIRPα
interaction
with
CD47-specific
antibody
significantly
enhances
macrophage
phagocytosis.
However,
concerns
regarding
their
toxicity
to
nontumor
cells
remain
substantial.
Here,
we
engineered
chimeric
antigen
receptor
macrophages
(CAR-Ms)
by
fusing
humanized
single-chain
variable
fragment
FcγRIIa
and
integrating
short
hairpin
RNA
silence
SIRPα,
thereby
disrupting
signaling
pathway.
These
modified
CAR-shSIRPα-M
exhibited
an
M1-like
phenotype,
superior
phagocytic
function,
substantial
cytotoxic
effects
on
HER2-positive
tumor
cells,
ability
eliminate
patient-derived
organoids.
In
vivo,
CAR-M
inhibited
growth
prolonged
survival
in
tumor-bearing
mice.
Notably,
enhanced
T-cell
infiltration
into
tumors,
enhancing
antitumor
response
both
immune
system
mouse
model
immunocompetent
Mechanistically,
SIRPα
inhibition
activated
inflammatory
pathways
cGAS-STING
cascade
leading
increased
production
proinflammatory
cytokines,
reactive
oxygen
species,
nitric
oxide,
effects.
findings
underscore
novel
strategy
increase
efficacy
immunotherapy,
particularly
against
solid
tumors.
Molecular Cancer Therapeutics,
Год журнала:
2024,
Номер
23(6), С. 780 - 790
Опубликована: Фев. 2, 2024
Hepatocellular
carcinoma
(HCC)
is
a
malignant
tumor
with
complex
and
diverse
immunosuppressive
microenvironment.
Tumor-associated
macrophages
(TAM)
are
an
essential
component
of
the
immune
TAMs
typically
exist
in
two
primary
states:
anti-tumor
M1
protumor
M2
macrophages.
Remarkably,
possess
high
plasticity,
enabling
them
to
switch
between
different
subtypes
or
alter
their
biological
functions
response
Based
on
research
into
role
occurrence
development
tumors,
including
HCC,
emerging
as
promising
targets
for
novel
treatment
strategies.
In
this
review,
we
provide
detailed
introduction
origin
TAMs,
elucidate
interactions
other
cells
microenvironment
describe
roles,
characteristics,
mechanisms
progression
HCC.
Furthermore,
furnish
overview
latest
therapeutic
strategies
targeting
TAMs.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 11, 2024
Chimeric
antigen
receptor
(CAR)
T
cell
therapy
has
transformed
cancer
immunotherapy.
However,
significant
challenges
limit
its
application
beyond
B
cell-driven
malignancies,
including
limited
clinical
efficacy,
high
toxicity,
and
complex
autologous
product
manufacturing.
Despite
efforts
to
improve
CAR
outcomes,
there
is
a
growing
interest
in
utilizing
alternative
immune
cells
develop
cells.
These
offer
several
advantages,
such
as
major
histocompatibility
(MHC)-independent
function,
tumor
microenvironment
(TME)
modulation,
increased
tissue
infiltration
capabilities.
Currently,
products
from
various
subtypes,
innate
cells,
hematopoietic
progenitor
even
exosomes
are
being
explored.
often
show
enhanced
antitumor
diminished
superior
penetration.
With
these
benefits
mind,
numerous
trials
underway
access
the
potential
of
innovative
This
review
aims
thoroughly
examine
challenges,
existing
insights
on
new
treatment.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 7, 2024
Abstract
Chimeric
Antigen
Receptor
(CAR)
T
cell
therapy
has
shown
promise
in
treating
hematologic
malignancies.
However,
it
is
limited
to
individualized
and
faces
challenges,
including
high
costs,
extended
preparation
time,
efficacy
against
solid
tumors.
Here,
we
generated
circular
RNAs
(circRNAs)
encoding
transmembrane
proteins,
referred
as
circRNA
CAR
,
which
mediated
remarkable
tumor
killing
both
cells
macrophages.
In
addition,
macrophages
exhibited
efficient
phagocytosis
of
pro-inflammatory
polarization
induced
by
vitro
.
We
demonstrated
that
delivered
with
immunocyte-tropic
lipid
nanoparticles
(LNPs),
significantly
inhibited
growth,
improved
survival
rates
a
microenvironment
mice.
Importantly,
the
combination
Anti-HER2-CAR
circRNA-based
cancer
vaccines
corresponding
HER2
antigen,
termed
synergistically
enhanced
anti-tumor
activity.
This
proof-of-concept
study
vivo
vaccines,
CAR-VAC,
holds
potential
become
an
upgraded
off-the-shelf
immunotherapy.
Cancer-associated
myeloid
cells
due
to
their
plasticity
play
dual
roles
in
both
promoting
and
inhibiting
tumor
progression.
Myeloid
with
immunosuppressive
properties
a
critical
role
anti-cancer
immune
regulation.
Cells
of
different
origin,
such
as
associated
macrophages
(TAMs),
neutrophils
(TANs),
derived
suppressor
(also
called
MDSCs)
eosinophils
are
often
expanded
cancer
patients
significantly
influence
survival,
but
also
the
outcome
therapies.
For
this
reason,
variety
preclinical
clinical
studies
modulate
activity
these
have
been
conducted,
however
without
successful
date.
In
review,
pro-tumor
cells,
cell-specific
therapeutic
targets,
vivo
on
cell
re-polarization
impact
immunotherapies/genetic
engineering
addressed.
This
paper
summarizes
ongoing
trials
concept
chimeric
antigen
receptor
macrophage
(CAR-M)
therapies,
suggests
future
research
perspectives,
offering
new
opportunities
development
novel
treatment
strategies.
