Background:
Immunotherapy
strategies
have
demonstrated
promising
efficacy
in
treating
various
cancers.
However,
cancer
cells
often
evade
immune
surveillance
by
reducing
their
immunogenicity,
which
limits
cell
infiltration
into
the
tumor
microenvironment.
Pyroptosis,
a
proinflammatory
form
of
programmed
death,
is
characterized
formation
plasma
membrane
pores
that
lead
to
release
intracellular
contents
and
stimulate
robust
response.
Results:
To
exploit
this
mechanism,
we
developed
hematoporphyrin
monomethyl
ether
(HMME)-loaded
nanoliposomes
capable
efficiently
accumulating
at
site.
Upon
ultrasound
irradiation,
these
nanomedicines
generate
reactive
oxygen
species
(ROS)
activate
Caspase-3,
cleaves
Gasdermin
E
(GSDME)
induces
pyroptosis.
Notably,
sonodynamic
therapy
(SDT)
based
on
nanosonosensitizers
enhanced
targeted
enrichment
chimeric
antigen
receptor
(CAR)-engineered
natural
killer
(NK)
ultrasound-irradiated
site,
significantly
improved
response,
effectively
inhibited
growth
proliferation
oral
squamous
carcinoma
(OSCC)
both
vivo
vitro.
Conclusions:
Given
NK
immunotherapy
has
an
excellent
safety
profile
with
minimal
risks
cytokine
syndrome
neurotoxicity,
approach
holds
promise
as
adjunct
cell-based
immunotherapies
through
SDT-induced
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Nov. 24, 2023
Natural
killer
(NK)
cells
are
cellular
components
of
the
innate
immune
system
that
can
recognize
and
suppress
proliferation
cancer
cells.
NK
eliminate
through
direct
lysis,
by
secreting
perforin
granzymes,
or
antibody-dependent
cell-mediated
cytotoxicity
(ADCC).
ADCC
involves
binding
Fc
gamma
receptor
IIIa
(CD16),
present
on
cells,
to
constant
region
an
antibody
already
bound
Cancer
use
several
mechanisms
evade
antitumor
activity
including
accumulation
inhibitory
cytokines,
recruitment
expansion
suppressor
such
as
myeloid-derived
(MDSCs)
regulatory
T
(Tregs),
modulation
ligands
for
receptors.
Several
strategies
have
been
developed
enhance
with
goal
overcoming
resistance
The
three
main
engineer
boost
include
boosting
modulatory
adoptive
cell
therapy,
employment
engineered
antibody-based
immunotherapy.
Although
first
two
improved
efficacy
cell-based
there
still
some
limitations,
immune-related
adverse
events,
induction
immune-suppressive
further
killing.
One
strategy
overcome
these
issues
is
combination
monoclonal
antibodies
(mAbs)
mediate
potentiated
anti-cancer
activity.
advantage
using
mAbs
they
activate
but
also
favor
effector
tumor
microenvironment
(TME).
clinical
trials
reported
combining
result
in
a
superior
response
compared
alone.
Next
generation
trials,
employing
higher
affinity
CD16
expressed
will
provide
more
effective
higher-quality
treatments
patients.
Cells,
Journal Year:
2024,
Volume and Issue:
13(3), P. 246 - 246
Published: Jan. 28, 2024
NKG2D
is
an
activating
receptor
of
natural
killer
cells
that
recognizes
stress-induced
ligands
(NKG2DL)
expressed
by
many
tumor
cells.
Nevertheless,
NKG2DL
downregulation
or
shedding
can
still
allow
cancer
to
evade
immune
surveillance.
Here,
we
used
lentiviral
gene
transfer
engineer
clinically
usable
NK-92
with
a
chimeric
antigen
(NKAR)
which
contains
the
extracellular
domain
for
target
recognition,
NKAR,
together
IL-15
superagonist
RD-IL15,
and
combined
these
effector
recombinant
NKG2D-interacting
bispecific
engagers
simultaneously
recognize
tumor-associated
antigens
epidermal
growth
factor
(EGFR)
ErbB2
(HER2).
Applied
individually,
in
vitro
cell-killing
assays,
NKAB-EGFR
NKAB-ErbB2
antibodies
specifically
redirected
NKAR-NK-92
NKAR_RD-IL15-NK-92
glioblastoma
other
elevated
EGFR
levels.
However,
mixed
cell
cultures,
as
model
heterogeneous
expression,
NKAR-NK
only
lysed
EGFR-
ErbB2-expressing
subpopulations
presence
one
NKAB
molecules.
This
was
circumvented
applying
together,
resulting
effective
antitumor
activity
similar
against
expressing
both
antigens.
Our
results
demonstrate
combining
NK
carrying
NKAR
allows
flexible
targeting,
enhance
tumor-antigen-specific
cytotoxicity
prevent
escape.
Chinese Journal of Cancer Research,
Journal Year:
2024,
Volume and Issue:
36(1), P. 1 - 16
Published: Jan. 1, 2024
Chimeric
antigen
receptor-natural
killer
(CAR-NK)
cells
have
emerged
as
another
prominent
player
in
the
realm
of
tumor
immunotherapy
following
CAR-T
cells.
The
unique
features
CAR-NK
make
it
possible
to
compensate
for
deficiencies
therapy,
such
complexity
manufacturing
process,
clinical
adverse
events,
and
solid
challenges.
To
date,
products
from
different
allogeneic
sources
exhibited
remarkable
anti-tumor
effects
on
preclinical
studies
gradually
been
applied
practice.
However,
each
source
has
advantages
disadvantages.
Selecting
a
suitable
may
help
maximize
cell
efficacy
increase
feasibility
transformation.
Therefore,
this
review
discusses
development
challenges
provide
reference
future
exploration.
Molecular Cancer,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: Oct. 23, 2024
Gastrointestinal
(GI)
cancers
represent
a
significant
health
burden
worldwide.
Their
incidence
continues
to
increase,
and
their
management
remains
clinical
challenge.
Chimeric
antigen
receptor
(CAR)
natural
killer
(NK)
cells
have
emerged
as
promising
alternative
CAR-T
for
immunotherapy
of
GI
cancers.
Notably,
CAR-NK
offer
several
advantages,
including
reduced
risk
graft-versus-host
disease,
lower
cytokine
release
syndrome,
the
ability
target
cancer
through
both
CAR-dependent
cytotoxic
mechanisms.
This
review
comprehensively
discusses
development
applications
in
treatment
We
explored
various
sources
NK
cells,
CAR
design
strategies,
current
state
cell
therapy
cancers,
highlighting
recent
preclinical
trials.
Additionally,
we
addressed
existing
challenges
propose
potential
strategies
enhance
efficacy
safety
therapy.
Our
findings
highlight
revolutionize
pave
way
future
applications.
Frontiers in Cell and Developmental Biology,
Journal Year:
2024,
Volume and Issue:
12
Published: Nov. 18, 2024
After
experiencing
many
ups
and
downs,
chimeric
antigen
receptor
(CAR)-T
cell
therapy
has
reached
a
milestone
as
an
anti-cancer
method,
evidenced
by
the
increasing
number
of
clinical
trials
approved
products.
Nonetheless,
there
is
real
need
to
optimize
CAR-T
overcome
its
existing
limitations.
The
importance
cellular
starting
material
for
generating
cells
undeniable,
current
personalized
manufacturing
approach
main
roadblock
providing
fast,
affordable,
standard
treatment
patients.
Thus,
developing
off-the-shelf
product
leading
focus
in
adoptive
therapy.
Several
biotech
companies
worldwide
are
focused
on
from
allogeneic
sources.
Induced
pluripotent
stem
(iPSCs)
have
unique
characteristics,
making
them
highly
attractive
among
various
IPSCs
can
be
modified
with
CAR,
undergo
other
intended
gene
manipulations,
then
differentiated
into
functional
hematopoietic
lineages
activity.
Moreover,
iPSCs
provide
unlimited
source,
simplifying
setting
protocol
homogenous
population
resulting
reducing
batch-to-batch
inconsistency.
In
this
review,
we
delve
iPSC-derived
(iCAR-T)
discuss
path
challenges
their
translation.
We
also
introduce
some
alternatives
conventional
iCAR-αβ-T
cells,
including
iCAR-T
limited
TCR
diversity,
iCAR-NK,
iCAR-macrophages,
iCAR-neutrophils
relative
advantages
disadvantages
well
differentiation
compliance
cGMP.
Finally,
reviewed
CAR-engineered
being
evaluated
trials.
Cells,
Journal Year:
2025,
Volume and Issue:
14(1), P. 53 - 53
Published: Jan. 5, 2025
The
overall
goal
of
this
work
was
to
assess
the
ability
Natural
Killer
cells
kill
cultures
patient-derived
glioblastoma
cells.
Herein
we
report
impressive
levels
NK-92
mediated
killing
various
observed
at
ET
(effector:
target)
ratios
5:1
and
1:1.
This
enabled
direct
comparison
degree
cell
loss
across
a
broader
range
cultures.
Importantly,
even
high
5:1,
there
are
always
subpopulations
that
prove
very
challenging
evade
Of
value
in
study
has
been
application
ECIS
(Electric
Cell–Substrate
Impedance
Sensing)
biosensor
technology
monitor
real-time,
enabling
temporal
assessment
powerful
revealing
higher
ratios,
acutely
sensitive
cells,
death
is
supported
by
high-content
imaging
data.
Moreover,
long-term
experiments
reveal
surviving
were
then
able
grow
reseed
culture,
which
evident
300–500
h
after
addition
for
multiple
lines.
In
addition,
our
provides
evidence
some
appear
be
compromised
early,
would
consistent
with
potent
evasive
mechanisms
tumour
research
strongly
highlights
potential
basis
identify
mechanism
utilised
now
need
target
achieve
maximal
cytolysis
resistant
It
survival
highly
clones
results
relapse.
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(3)
Published: Jan. 15, 2025
Induction
of
senescence
by
chemotherapeutic
agents
arrests
cancer
cells
and
activates
immune
surveillance
responses
to
contribute
therapy
outcomes.
In
this
investigation,
we
searched
for
ways
enhance
the
NK-mediated
elimination
senescent
cells.
We
used
a
staggered
screen
approach,
first
identifying
siRNAs
potentiating
secretion
immunomodulatory
cytokines
later
test
their
ability
killing
identified
that
genetic
or
pharmacological
inhibition
SMARCA4
enhanced
cell
NK
expression
is
elevated
during
its
derepresses
repetitive
elements,
inducing
SASP
via
activation
cGAS/STING
MAVS/MDA5
pathways.
Moreover,
PROTAC
targeting
synergized
with
cisplatin
increase
infiltration
CD8
T
mature,
activated
in
an
immunocompetent
model
ovarian
cancer.
Our
results
indicate
inhibitors
may
represent
senotherapeutic
interventions
Cancer Immunology Immunotherapy,
Journal Year:
2025,
Volume and Issue:
74(3)
Published: Feb. 4, 2025
Abstract
Mortality
and
recurrence
rates
of
hepatocellular
carcinoma
(HCC)
remain
high
despite
the
use
various
treatment
methods.
Recently,
cell-based
immunotherapy
using
natural
killer
(NK)
cells
has
attracted
considerable
attention
in
cancer
immunotherapy.
NK
generated
from
induced
pluripotent
stem
(iPSCs)
are
a
new
option
for
as
an
cell
resource.
The
eNK
(HLCN061,
developed
by
HEALIOS
K.K.)
human
iPSC-derived
differentiated
clinical-grade
iPSCs
which
IL-15,
CCR2B,
CCL19,
CD16a,
NKG2D
have
been
introduced.
In
this
study,
we
aimed
to
evaluate
potential
therapy
HCC
treatment.
analysis
surface
intracellular
molecules
revealed
that
antitumor-related
(TRAIL,
CD226,
CD16)
cytotoxic
factors
(perforin,
granzyme
B,
TNFα,
IFNγ)
were
highly
expressed.
addition,
exhibited
cytotoxicity
against
lines
(HepG2,
HuH7,
SNU-423),
sensitive
NKG2D,
TRAIL,
CD226.
TRAIL
perforin/granzyme
B
pathways
largely
involved
mechanism,
indicated
reduction
inhibitory
antibodies
concanamycin
A,
inhibits
B-mediated
cytotoxicity.
Our
data
suggest
cells,
whose
functions
enhanced
genetic
engineering,
improve
