Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Сен. 5, 2024
Chimeric
antigen
receptor
(CAR)
T-cell
therapy
has
revolutionized
the
treatment
of
hematologic
malignancies,
offering
remarkable
remission
rates
in
otherwise
refractory
conditions.
However,
its
expansion
into
broader
oncological
applications
faces
significant
hurdles,
including
limited
efficacy
solid
tumors,
safety
concerns
related
to
toxicity,
and
logistical
challenges
manufacturing
scalability.
This
review
critically
examines
latest
advancements
aimed
at
overcoming
these
obstacles,
highlighting
innovations
CAR
engineering,
novel
targeting
strategies,
improvements
delivery
persistence
within
tumor
microenvironment.
We
also
discuss
development
allogeneic
T
cells
as
off-the-shelf
therapies,
strategies
mitigate
adverse
effects,
integration
with
other
therapeutic
modalities.
comprehensive
analysis
underscores
synergistic
potential
enhance
safety,
efficacy,
accessibility
providing
a
forward-looking
perspective
on
their
evolutionary
trajectory
cancer
treatment.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Окт. 7, 2024
Abstract
Colorectal
cancer
(CRC)
remains
one
of
the
leading
causes
cancer-related
mortality
worldwide.
Its
complexity
is
influenced
by
various
signal
transduction
networks
that
govern
cellular
proliferation,
survival,
differentiation,
and
apoptosis.
The
pathogenesis
CRC
a
testament
to
dysregulation
these
signaling
cascades,
which
culminates
in
malignant
transformation
colonic
epithelium.
This
review
aims
dissect
foundational
mechanisms
implicated
CRC,
elucidate
generalized
principles
underpinning
neoplastic
evolution
progression.
We
discuss
molecular
hallmarks
including
genomic,
epigenomic
microbial
features
highlight
role
orchestration
tumorigenic
process.
Concurrently,
we
advent
targeted
immune
therapies
assessing
their
impact
on
current
clinical
landscape.
development
has
been
informed
deepening
understanding
oncogenic
signaling,
identification
key
nodes
within
can
be
exploited
pharmacologically.
Furthermore,
explore
potential
integrating
AI
enhance
precision
therapeutic
targeting
patient
stratification,
emphasizing
personalized
medicine.
In
summary,
our
captures
dynamic
interplay
between
aberrant
concerted
efforts
counteract
changes
through
strategies,
ultimately
aiming
pave
way
for
improved
prognosis
treatment
modalities
colorectal
cancer.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(44)
Опубликована: Авг. 31, 2023
Abstract
Chimeric
Antigen
Receptor
(CAR)
T
cell
immunotherapy
is
revolutionizing
treatment
for
patients
suffering
from
B‐cell
lymphoma
(BL).
However,
the
current
method
of
CAR
production
complicated
and
expensive,
requiring
collection
patient
blood
to
enrich
population,
ex
vivo
engineering/activation,
quality
assessment
before
can
receive
treatment.
Herein
we
leverage
Spleen
Selective
ORgan
Targeted
(SORT)
Lipid
Nanoparticles
(LNPs)
produce
cells
in
situ
bypass
extensive
laborious
process
currently
used.
Optimized
SORT
LNPs
containing
10
%
18
:
1
PA
transfected
CD3+,
CD8+,
CD4+
wild‐type
mice.
delivered
Cre
recombinase
mRNA
encoding
reporter
mice
a
lymphoreplete
B
model
(respectively)
after
intravenous
injection
without
need
active
targeting
ligands.
Moreover,
increased
overall
survival
with
less
aggressive
form
lymphoma.
In
addition,
reduced
tumor
metastasis
liver
by
increasing
infiltrating
lymphocytes.
Overall,
these
results
offer
promising
alternative
pre‐clinical
potential
treat
hematological
malignancies.
Cellular and Molecular Immunology,
Год журнала:
2024,
Номер
21(10), С. 1089 - 1108
Опубликована: Авг. 12, 2024
Abstract
In
the
past
decade,
chimeric
antigen
receptor
(CAR)-T
cell
therapy
has
emerged
as
a
promising
immunotherapeutic
approach
for
combating
cancers,
demonstrating
remarkable
efficacy
in
relapsed/refractory
hematological
malignancies
both
pediatric
and
adult
patients.
CAR-natural
killer
(CAR-NK)
complements
CAR-T
by
offering
several
distinct
advantages.
CAR-NK
cells
do
not
require
HLA
compatibility
exhibit
low
safety
concerns.
Moreover,
are
conducive
to
“off-the-shelf”
therapeutics,
providing
significant
logistic
advantages
over
cells.
Both
have
shown
consistent
results
malignancies.
However,
their
against
solid
tumors
remains
limited
due
various
obstacles
including
tumor
trafficking
infiltration,
well
an
immuno-suppressive
microenvironment.
this
review,
we
discuss
recent
advances
current
challenges
of
immunotherapies,
with
specific
focus
on
application
tumors.
We
also
analyze
depth
drawbacks
compared
highlight
CAR
optimization.
Finally,
explore
future
perspectives
these
adoptive
highlighting
increasing
contribution
cutting-edge
biotechnological
tools
shaping
next
generation
cellular
immunotherapy.
World Journal of Clinical Oncology,
Год журнала:
2024,
Номер
15(9), С. 1136 - 1156
Опубликована: Авг. 29, 2024
Colorectal
cancer
(CRC)
is
the
third
most
common
worldwide,
and
second
cause
of
cancer-related
death.
In
2020,
estimated
number
deaths
due
to
CRC
was
approximately
930000,
accounting
for
10%
all
worldwide.
Accordingly,
there
a
vast
amount
ongoing
research
aiming
find
new
improved
treatment
modalities
that
can
potentially
increase
survival
decrease
overall
morbidity
mortality.
Current
management
strategies
include
surgical
procedures
resectable
cases,
radiotherapy,
chemotherapy,
immunotherapy,
in
addition
their
combination,
non-resectable
tumors.
Despite
these
options,
remains
incurable
50%
cases.
Nonetheless,
significant
improvements
techniques
have
allowed
approaches
be
frequently
updated,
leading
availability
drugs
therapeutic
strategies.
This
review
summarizes
recent
CRC,
with
special
emphasis
on
are
currently
being
studied
great
potential
improve
prognosis
lifespan
patients
CRC.
Journal of Hematology & Oncology,
Год журнала:
2025,
Номер
18(1)
Опубликована: Янв. 13, 2025
The
tumor
microenvironment
(TME)
is
integral
to
cancer
progression,
impacting
metastasis
and
treatment
response.
It
consists
of
diverse
cell
types,
extracellular
matrix
components,
signaling
molecules
that
interact
promote
growth
therapeutic
resistance.
Elucidating
the
intricate
interactions
between
cells
TME
crucial
in
understanding
progression
challenges.
A
critical
process
induced
by
epithelial-mesenchymal
transition
(EMT),
wherein
epithelial
acquire
mesenchymal
traits,
which
enhance
their
motility
invasiveness
progression.
By
targeting
various
components
TME,
novel
investigational
strategies
aim
disrupt
TME's
contribution
EMT,
thereby
improving
efficacy,
addressing
resistance,
offering
a
nuanced
approach
therapy.
This
review
scrutinizes
key
players
emphasizing
avenues
therapeutically
components.
Moreover,
article
discusses
implications
for
resistance
mechanisms
highlights
current
toward
modulation
along
with
potential
caveats.
Cells,
Год журнала:
2024,
Номер
13(2), С. 146 - 146
Опубликована: Янв. 12, 2024
This
last
decade,
chimeric
antigen
receptor
(CAR)
T-cell
therapy
has
become
a
real
treatment
option
for
patients
with
B-cell
malignancies,
while
multiple
efforts
are
being
made
to
extend
this
other
malignancies
and
broader
patient
populations.
However,
several
limitations
remain,
including
those
associated
the
time-consuming
highly
personalized
manufacturing
of
autologous
CAR-Ts.
Technologies
establish
"off-the-shelf"
allogeneic
CAR-Ts
low
alloreactivity
currently
developed,
strong
focus
on
gene-editing
technologies.
Although
these
technologies
have
many
advantages,
they
also
limitations,
double-strand
breaks
in
DNA
safety
risks
as
well
lack
modulation.
As
an
alternative,
non-gene-editing
provide
interesting
approach
support
development
future,
possibilities
fine-tuning
gene
expression
easy
development.
Here,
we
will
review
different
ways
can
be
manufactured
discuss
which
used.
The
biggest
hurdles
successful
summarized,
finally,
overview
current
clinical
evidence
comparison
its
counterpart
given.
EClinicalMedicine,
Год журнала:
2024,
Номер
73, С. 102684 - 102684
Опубликована: Июнь 20, 2024
The
FDA's
alerts
regarding
the
T-cell
lymphoma
risk
post
CAR-T
therapy
has
garnered
global
attention,
yet
a
comprehensive
profile
of
second
primary
malignancies
(SPMs)
following
treatment
is
lacking.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Июль 10, 2024
Abstract
Cancer
immunotherapy
harnesses
the
body’s
immune
system
to
combat
malignancies,
building
upon
an
understanding
of
tumor
immunosurveillance
and
evasion
mechanisms.
This
therapeutic
approach
reactivates
anti-tumor
responses
can
be
categorized
into
active,
passive,
combined
immunization
strategies.
Active
engages
recognize
attack
cells
by
leveraging
host
immunity
with
cytokine
supplementation
or
vaccination.
Conversely,
passive
employs
exogenous
agents,
such
as
monoclonal
antibodies
(anti-CTLA4,
anti-PD1,
anti-PD-L1)
adoptive
cell
transfers
(ACT)
genetically
engineered
chimeric
antigen
receptor
(CAR)
T
NK
cells,
exert
effects.
Over
past
decades,
CAR-T
therapies
have
gained
significant
traction
in
oncological
treatment,
offering
hope
through
their
targeted
approach.
However,
potential
adverse
effects
associated
including
release
syndrome
(CRS),
off-tumor
toxicity,
neurotoxicity,
warrant
careful
consideration.
Recently,
CAR-NK
therapy
has
emerged
a
promising
alternative
landscape
immunotherapy,
distinguished
its
innate
advantages
over
modalities.
In
this
review,
we
will
synthesize
latest
research
clinical
advancements
therapies.
We
elucidate
benefits
employing
oncology
critically
examine
developmental
bottlenecks
impeding
broader
application.
Our
discussion
aims
provide
comprehensive
overview
current
status
future
cancer
immunotherapy.