Expert Review of Anticancer Therapy,
Год журнала:
2024,
Номер
unknown, С. 1 - 17
Опубликована: Окт. 28, 2024
Introduction
Adoptive
immunotherapy
using
chimeric
antigen
receptor
(CAR)-engineered
T
cells
has
proven
transformative
in
the
management
of
B
cell
and
plasma
cel
derived
malignancies.
However,
solid
tumors
have
largely
to
be
resistant
this
therapeutic
modality.
Challenges
include
paucity
safe
target
antigens,
heterogeneity
expression
within
tumor,
difficulty
delivery
CAR
site
disease,
poor
penetration
tumor
deposits
inability
circumvent
array
immunosuppressive
biophysical
barriers
imposed
by
microenvironment.
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.
Biomedicines,
Год журнала:
2025,
Номер
13(1), С. 98 - 98
Опубликована: Янв. 3, 2025
The
incidence
rate
of
cutaneous
melanoma
is
on
the
rise
worldwide,
due
to
increased
exposure
UV
radiation,
aging
populations,
and
teratogen
agents.
However,
diagnosis
more
precise,
number
new
cases
related
improved
tools.
Despite
better
early
therapies,
has
remained
a
significant
public
health
challenge
because
its
aggressive
behavior
high
potential
for
metastasis.
In
2020,
constituted
approximately
1.3%
all
cancer
deaths
that
occurred
within
European
Union,
thereby
highlighting
necessity
effective
prevention,
timely
diagnosis,
sustainable
treatment
measures,
especially
as
growing
occur
among
younger
patients.
Melanoma
regarded
one
most
inflamed
cancers
immune
cell
presence
strong
response
immunotherapy,
fueling
need
development
immune-driven
innovative
treatments.
Approved
including
checkpoint
inhibitors
(e.g.,
anti-PD-1
anti-CTLA-4),
have
notably
survival
rates
in
melanoma.
limitations
PD-1/PD-L1
CTLA-4
axes
inhibitors,
such
low
rates,
resistance,
toxicity,
driven
continued
research
advancements
strategies.
Current
clinical
trials
are
exploring
various
combinations
with
costimulatory
receptor
agonists,
chemotherapy,
targeted
other
immunotherapies,
goal
improving
outcomes
reducing
side
effects
Emerging
approaches,
adoptive
therapy
tumor-infiltrating
lymphocytes
(TILs)
oncolytic
virotherapy,
showing
promise.
While
CAR-T
been
less
successful
compared
blood
cancers,
ongoing
addressing
challenges
like
tumor
microenvironment
antigen
specificity.
This
review
provides
an
overview
requirement
advances
these
medications,
mark
step
forward
management,
set
bring
fresh
breath
hope
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.
Annals of Hematology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 17, 2025
Abstract
Refractory
Diffuse
Large
B-cell
Lymphoma
(DLBCL)
presents
a
major
therapeutic
challenge
due
to
its
resistance
standard
treatments.
Engineered
T-cells,
especially
Chimeric
Antigen
Receptor
(CAR)
have
shown
promise
in
overcoming
drug
resistance.
This
study
investigates
the
effectiveness
of
WEE1-engineered
T-cells
targeting
and
eliminating
refractory
DLBCL
vitro.
CAR
were
created
by
transducing
5th-generation
construct
designed
recognize
WEE1,
surface
antigen
commonly
found
on
cells.
The
cytotoxic
effect
engineered
was
tested
against
Rituximab-resistant
cells
(RR-NU-DUL-1).
Apoptosis
cell
cycle
evaluated
using
flow
cytometry.
Quantitative
Real-time
PCR
(RT-PCR)
used
measure
expression
BCL2,
CDK2.
results
showed
significant
increase
target
lysis,
apoptosis,
necrosis,
reduction
percentage
G2M
phase
cycle,
as
well
decrease
gene
level,
indicating
strong
anti-tumor
activity.
These
findings
suggest
that
T-cell
therapy
holds
great
for
treating
DLBCL,
offering
potential
path
clinical
application.
vitro
evaluation
highlights
targeted
treatment
strategy
emphasizing
their
applicability
ability
overcome
mechanisms
this
aggressive
lymphoma
subtype.
Journal of Clinical Medicine,
Год журнала:
2025,
Номер
14(2), С. 327 - 327
Опубликована: Янв. 8, 2025
Multiple
Myeloma
(MM)
is
a
complex
hematological
malignancy
characterized
by
the
clonal
proliferation
of
malignant
plasma
cells
within
bone
marrow
(BM)
[...].
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 10, 2025
Over
the
past
decades,
significant
progress
has
been
made
in
understanding
of
non-small
cell
lung
cancer
(NSCLC)
biology
and
tumor
progression
mechanisms,
resulting
development
novel
strategies
for
early
detection
wide-ranging
care
approaches.
Since
their
introduction,
over
20
years
ago,
targeted
therapies
with
tyrosine
kinase
inhibitors
(TKIs)
have
revolutionized
treatment
landscape
NSCLC.
Nowadays,
remain
gold
standard
many
patients,
but
still
they
suffer
from
adverse
effects,
including
unexpected
toxicity
intrinsic
acquired
resistance
mutations,
which
lead
to
relapse.
The
adoption
immune
checkpoint
(ICIs)
2015,
offered
exceptional
survival
benefits
patients
without
targetable
alterations.
Despite
this
notable
progress,
challenges
remain,
as
not
all
respond
favorably
ICIs,
therapy
can
develop
time.
A
crucial
factor
influencing
clinical
response
immunotherapy
is
microenvironment
(TME).
TME
pivotal
orchestrating
interactions
between
neoplastic
cells
system,
growth
outcomes.
In
review,
we
discuss
how
intricate
relationship
success
survey
current
state
intervention,
a
focus
on
forthcoming
promising
chimeric
antigen
receptor
(CAR)
T
sets
major
obstacles
CAR-T
therapies,
creating
conditions
that
suppress
response,
inducing
exhaustion.
To
enhance
efficacy,
specific
efforts
associated
NSCLC,
should
definitely
TME-related
immunosuppression
escape
by
combining
blockades.
Cell Death Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Фев. 10, 2025
Abstract
One
of
the
most
promising
cancer
immunotherapies
is
based
on
bi-specific
T-cell
engagers
(BiTEs)
that
simultaneously
bind
with
one
arm
to
a
tumor-associated
antigen
tumor
cells
and
other
CD3
complex
T
form
TCR-MHC
independent
immune
synapse.
We
previously
generated
four
novel
tri-specific
tribodies
made
up
Fab
targeting
5T4,
an
oncofetal
expressed
several
types
tumors,
scFv
cells,
additional
specific
for
checkpoint
(IC),
such
as
PD-1,
PD-L1
or
LAG-3.
To
verify
their
advantages
over
combinations
BiTEs
(CD3/TAA)
IC
inhibitors,
recently
used
overcome
immunosuppressive
environment,
here
we
tested
functional
properties
in
comparison
clinically
validated
mAbs
same
ICs,
alone
combination
control
devoid
immunomodulatory
scFvs,
called
53
P.
found
activated
human
peripheral
blood
mononuclear
more
efficiently
than
(atezolizumab,
pembrolizumab,
relatlimab)
either
P,
leading
stronger
cytotoxicity
cytokines
release.
In
particular,
53L10
tribody
displayed
much
potent
effects
P
all
led
complete
regression
vivo,
showing
higher
efficacy
atezolizumab.
shed
light
molecular
basis
this
potentiated
anti-tumor
activity
by
evidencing
insertion
anti-PD-L1
moiety
not
only
binding
but
also
blocked
increased
induced
IFNγ
secretion
due
activation.
These
results
are
important
design
antigens.
Frontiers in Bioscience-Landmark,
Год журнала:
2024,
Номер
29(11)
Опубликована: Ноя. 8, 2024
Regulatory
T-cells
(Tregs)
play
a
crucial
role
in
maintaining
immune
homeostasis,
ensuring
balanced
response.
Tregs
primarily
operate
an
antigen-specific
fashion,
facilitated
by
their
distinct
distribution
within
discrete
niches.
have
been
studied
extensively,
from
point
of
origin
the
thymus
to
fate
periphery
or
organs.
Signals
received
antigen-presenting
cells
(APCs)
stimulate
dampen
inflammation.
Almost
all
tumors
are
characterized
pathological
abundance
suppression
microenvironment.
Conversely,
lack
thereof
proves
detrimental
immunological
disorders.
Achieving
expression
relation
other
compartments
is
important
establishing
effective
and
adaptable
tolerance
towards
cancer
autoantigens.
In
context
cancer,
it
essential
decrease
frequency
overcome
tumor
suppression.
A
lower
survival
rate
associated
with
presence
excessive
exhausted
effector
increased
regulatory
cells.
However,
when
comes
treating
graft
rejection
autoimmune
diseases,
focus
lies
on
transfer
Tregs.
Here,
we
explore
complex
mechanisms
that
use
human
disease
balance
Deleted Journal,
Год журнала:
2024,
Номер
32(4), С. 200891 - 200891
Опубликована: Окт. 5, 2024
Chimeric
antigen
receptor
(CAR)
T
cell
therapy
has
encountered
limited
success
in
solid
tumors.
The
lack
of
dependable
antigens
and
the
immunosuppressive
tumor
microenvironment
(TME)
are
major
challenges.
Within
TME,
cells
along
with
employ
an
immune-evasion
mechanism
that
upregulates
programmed
death
ligand
1
(PD-L1)
to
deactivate
effector
cells;
this
makes
PD-L1
a
reliable,
universal
target
for
We
developed
novel
CAR
(MC9999)
using
our
humanized
anti-PD-L1
monoclonal
antibody,
designed
simultaneously
cells.
antigen-specific
antitumor
effects
MC9999
were
observed
consistently
across
four
models:
breast
cancer,
lung
melanoma,
glioblastoma
multiforme
(GBM).
Notably,
intravenous
administration
eradicated
intracranially
established
LN229
GBM
tumors,
suggesting
penetration
blood-brain
barrier.
proof-of-concept
data
demonstrate
cytolytic
effect
against
cells,
including
microglia
HMC3
M2
macrophages.
Furthermore,
elicited
cytotoxicity
primary
tumor-associated
macrophages
within
concept
targeting
both
was
further
validated
derived
from
cancer
patients.
These
findings
establish
as
foundation
development
effective
therapies