Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology
Emile M. Youssef,
Brandon Fletcher,
Dannelle Palmer
и другие.
Frontiers in Medicine,
Год журнала:
2025,
Номер
11
Опубликована: Янв. 13, 2025
Gene
therapy
has
long
been
a
cornerstone
in
the
treatment
of
rare
diseases
and
genetic
disorders,
offering
targeted
solutions
to
conditions
once
considered
untreatable.
As
field
advances,
its
transformative
potential
is
now
expanding
into
oncology,
where
personalized
therapies
address
immune-related
complexities
cancer.
This
review
highlights
innovative
therapeutic
strategies,
including
gene
replacement,
silencing,
oncolytic
virotherapy,
CAR-T
cell
therapy,
CRISPR-Cas9
editing,
with
focus
on
their
application
both
hematologic
malignancies
solid
tumors.
CRISPR-Cas9,
revolutionary
tool
precision
medicine,
enables
precise
editing
cancer-driving
mutations,
enhancing
immune
responses
disrupting
tumor
growth
mechanisms.
Additionally,
emerging
approaches
target
ferroptosis—a
regulated,
iron-dependent
form
death—offering
new
possibilities
for
selectively
inducing
death
resistant
cancers.
Despite
significant
breakthroughs,
challenges
such
as
heterogeneity,
evasion,
immunosuppressive
microenvironment
(TME)
remain.
To
overcome
these
barriers,
novel
like
dual-targeting,
armored
cells,
combination
checkpoint
inhibitors
ferroptosis
inducers
are
being
explored.
rise
allogeneic
“off-the-shelf”
offers
scalable
more
accessible
options.
The
regulatory
landscape
evolving
accommodate
advancements,
frameworks
RMAT
(Regenerative
Medicine
Advanced
Therapy)
U.S.
ATMP
(Advanced
Therapy
Medicinal
Products)
Europe
fast-tracking
approval
therapies.
However,
ethical
considerations
surrounding
CRISPR-based
editing—such
off-target
effects,
germline
ensuring
equitable
access—remain
at
forefront,
requiring
ongoing
oversight.
Advances
non-viral
delivery
systems,
lipid
nanoparticles
(LNPs)
exosomes,
improving
safety
efficacy
By
integrating
innovations
addressing
concerns,
poised
revolutionize
cancer
treatment,
providing
durable,
effective,
Язык: Английский
Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy
Molecular Cancer,
Год журнала:
2024,
Номер
23(1)
Опубликована: Авг. 26, 2024
In
many
hematologic
malignancies,
the
adoptive
transfer
of
chimeric
antigen
receptor
(CAR)
T
cells
has
demonstrated
notable
success;
nevertheless,
further
improvements
are
necessary
to
optimize
treatment
efficacy.
Current
CAR-T
therapies
particularly
discouraging
for
solid
tumor
treatment.
The
immunosuppressive
microenvironment
tumors
affects
cells,
limiting
treatment's
effectiveness
and
safety.
Therefore,
enhancing
cell
infiltration
capacity
resolving
responses
within
could
boost
anti-tumor
effect.
Specific
strategies
include
structurally
altering
combined
with
targeted
therapy,
radiotherapy,
or
chemotherapy.
Overall,
monitoring
status
is
beneficial
in
investigating
viability
such
advancing
therapy.
Язык: Английский
The next frontier in immunotherapy: potential and challenges of CAR-macrophages
Experimental Hematology and Oncology,
Год журнала:
2024,
Номер
13(1)
Опубликована: Авг. 5, 2024
Abstract
Chimeric
antigen
receptor
macrophage
(CAR-MΦ)
represents
a
significant
advancement
in
immunotherapy,
especially
for
treating
solid
tumors
where
traditional
CAR-T
therapies
face
limitations.
CAR-MΦ
offers
promising
approach
to
target
and
eradicate
tumor
cells
by
utilizing
macrophages’
phagocytic
antigen-presenting
abilities.
However,
challenges
such
as
the
complex
microenvironment
(TME),
variability
expression,
immune
suppression
limit
their
efficacy.
This
review
addresses
these
issues,
exploring
mechanisms
of
action,
optimal
construct
designs,
interactions
within
TME.
It
also
delves
into
ex
vivo
manufacturing
CAR-MΦ,
discussing
autologous
allogeneic
sources
importance
stringent
quality
control.
The
potential
synergies
integrating
with
existing
cancer
like
checkpoint
inhibitors
conventional
chemotherapeutics
are
examined
highlight
possible
enhanced
treatment
outcomes.
Furthermore,
regulatory
pathways
scrutinized
alongside
established
protocols
cells,
identifying
unique
considerations
essential
clinical
trials
market
approval.
Proposed
safety
monitoring
frameworks
aim
manage
adverse
events,
cytokine
release
syndrome,
crucial
patient
safety.
Consolidating
current
research
insights,
this
seeks
refine
therapeutic
applications,
overcome
barriers,
suggest
future
directions
transition
from
experimental
platforms
standard
care
options.
Язык: Английский
Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells
Science Advances,
Год журнала:
2025,
Номер
11(2)
Опубликована: Янв. 10, 2025
Chimeric
antigen
receptor
T
cells
(CART)
targeting
CD19
through
CD28.ζ
signaling
induce
rapid
lysis
of
leukemic
blasts,
contrasting
with
persistent
tumor
control
exhibited
by
4-1BB.ζ-CART.
We
reasoned
that
molecular
dynamics
at
the
CART
immune
synapse
(CARIS)
could
explain
differences
in
their
rejection
kinetics.
observed
CD28.ζ-CART
engaged
brief
highly
lethal
CARIS
and
mastered
serial
killing,
whereas
4-1BB.ζ-CART
formed
lengthy
relied
on
robust
expansion
cooperative
killing.
analyzed
membrane
lipid
rafts
(mLRs)
found
that,
upon
engagement,
CD28.ζ-CAR
molecules
rapidly
but
transiently
translocated
into
mLRs,
mobilizing
microtubular
organizing
center
lytic
granules
to
CARIS.
This
enabled
fast
recovery
sensitivity
low
target
site
density.
In
contrast,
gradual
accumulation
4-1BB.ζ-CAR
LFA-1
mLRs
built
mechanically
tonic
mediating
chronic
Fas
ligand–based
The
CD28.ζ-
4-1BB.ζ-CARIS
distinct
cytolytic
behavior
can
guide
engineering
more
adaptive
effective
cellular
products.
Язык: Английский
CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY: HARNESSING EXTRACELLULAR VESICLES FOR ENHANCED EFFICACY
Pharmacological Research,
Год журнала:
2024,
Номер
208, С. 107352 - 107352
Опубликована: Авг. 13, 2024
A
cutting-edge
approach
in
cell-based
immunotherapy
for
combating
resistant
cancer
involves
genetically
engineered
chimeric
antigen
receptor
T
(CAR-T)
lymphocytes.
In
recent
years,
these
therapies
have
demonstrated
effectiveness,
leading
to
their
commercialization
and
clinical
application
against
certain
types
of
cancer.
However,
CAR-T
therapy
faces
limitations,
such
as
the
immunosuppressive
tumour
microenvironment
(TME)
that
can
render
cells
ineffective,
adverse
side
effects
therapy,
including
cytokine
release
syndrome
(CRS).
Extracellular
vesicles
(EVs)
are
a
diverse
group
membrane-bound
particles
released
into
extracellular
environment
by
virtually
all
cell
types.
They
essential
intercellular
communication,
transferring
cargoes
proteins,
lipids,
various
RNAs,
DNA
fragments
target
cells,
traversing
biological
barriers
both
locally
systemically.
EVs
play
roles
numerous
physiological
processes,
with
those
from
immune
non-immune
capable
modulating
system
through
activation
or
suppression.
Leveraging
this
capability
enhance
could
represent
significant
advancement
overcoming
its
current
limitations.
This
review
examines
landscape
explores
potential
role
augmenting
therapeutic
efficacy.
Язык: Английский
Evolving CAR T-Cell Therapy to Overcome the Barriers in Treating Pediatric Central Nervous System Tumors
Cancer Discovery,
Год журнала:
2025,
Номер
15(5), С. 890 - 902
Опубликована: Апрель 29, 2025
CNS
tumors
are
the
leading
cause
of
cancer-related
death
in
children,
highlighting
dire
need
for
new
treatment
strategies.
CAR
T
cells
represent
a
unique
approach,
distinct
from
cytotoxic
chemotherapies
and
small-molecule
inhibitors
that
have
dominated
clinical
trial
space
decades.
Phase
I
T-cell
trials
shown
feasibility
possible
efficacy
against
pediatric
tumors;
however,
many
challenges
must
be
overcome
if
these
therapeutics
going
to
beneficial
most
affected
children.
Although
rapid
translational
development
early-phase
quickly
evolved
our
understanding,
community
now
yearns
critical
assessments
open
dialogue
about
overcoming
remaining
obstacles
ahead.
Язык: Английский
Complex neural-immune interactions shape glioma immunotherapy
Immunity,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
Rich
neural-immune
interactions
in
the
central
nervous
system
(CNS)
shape
its
function
and
create
a
unique
immunological
microenvironment
for
immunotherapy
CNS
malignancies.
Far
from
now-debunked
concept
of
"immune
privilege,"
it
is
now
understood
that
niches
constant
immune
surveillance
brain
contribute
multifaceted
ways
to
health
robustly
influence
approaches
cancers.
Challenges
include
immune-suppressive
neurotoxicity-promoting
crosstalk
between
brain,
immune,
tumor
cells.
Developing
effective
immunotherapies
cancers
will
require
deeper
understanding
these
neural-immune-malignant
cell
interactions.
Here,
we
review
progress
challenges
gliomas
spinal
cord
light
highlight
future
work
needed
optimize
promising
gliomas.
Язык: Английский
CAR-T cells for H3K27-altered diffuse midline gliomas: where do we stand?
Immunotherapy,
Год журнала:
2024,
Номер
16(12), С. 775 - 778
Опубликована: Июль 3, 2024
Язык: Английский
Therapeutic advantage of combinatorial CAR T cell and chemo-therapies
Pharmacological Reviews,
Год журнала:
2024,
Номер
77(1), С. 100011 - 100011
Опубликована: Окт. 7, 2024
Chimeric
antigen
receptor
(CAR)
T
cell
therapies
have
transformed
outcomes
for
many
patients
with
hematological
malignancies.
However,
some
do
not
respond
to
CAR
treatment,
and
adapting
cells
solid
brain
tumors
has
been
met
challenges
including
a
hostile
tumor
microenvironment
poor
persistence.
Thus,
it
is
unlikely
that
therapy
alone
will
be
sufficient
consistent,
complete
clearance
across
cancer
patients.
Combinatorial
of
chemotherapeutics
are
promising
approach
overcoming
this
as
could
augment
improved
anti-tumor
activity
or
work
in
tandem
clear
tumors.
Herein,
we
review
efforts
towards
achieving
successful
chemical
drug
combination
therapies.
We
focus
on
approved
these
more
easily
translated
the
clinic,
but
also
non-approved
screens
designed
reveal
new
combinations.
Together,
highlights
promise
chemotherapy
combinations
specific
how
combinatorial
overcomes
faced
by
either
monotherapy
supports
potential
therapeutic
strategy
improve
Significance
Statement
Improving
currently
available
products
via
drastically
expand
types
cancers
number
benefit
from
when
neither
achieve
clearance.
provide
thorough
current
studying
perspectives
optimal
ways
identify
effective
moving
forward.
Язык: Английский