Surface Engineering of Natural Killer Cells with CD44‐targeting Ligands for Augmented Cancer Immunotherapy
Small,
Journal Year:
2023,
Volume and Issue:
20(24)
Published: Dec. 31, 2023
Abstract
Adoptive
immunotherapy
utilizing
natural
killer
(NK)
cells
has
demonstrated
remarkable
efficacy
in
treating
hematologic
malignancies.
However,
its
clinical
intervention
for
solid
tumors
is
hindered
by
the
limited
expression
of
tumor‐specific
antigens.
Herein,
lipid‐PEG
conjugated
hyaluronic
acid
(HA)
materials
(HA‐PEG‐Lipid)
simple
ex‐vivo
surface
coating
NK
developed
1)
lipid‐mediated
cellular
membrane
anchoring
via
hydrophobic
interaction
and
thereby
2)
sufficient
presentation
CD44
ligand
(i.e.,
HA)
onto
cancer
targeting,
without
need
genetic
manipulation.
Membrane‐engineered
can
selectively
recognize
CD44‐overexpressing
through
HA‐CD44
affinity
subsequently
induce
situ
activation
elimination.
Therefore,
surface‐engineered
using
HA‐PEG‐Lipid
(HANK
cells)
establish
an
immune
synapse
with
MIA
PaCa‐2
pancreatic
cells,
triggering
“recognition‐activation”
mechanism,
ultimately
eliminating
cells.
Moreover,
mouse
xenograft
tumor
models,
administrated
HANK
demonstrate
significant
infiltration
into
tumors,
resulting
apoptosis/necrosis
effective
suppression
progression
metastasis,
as
compared
to
gemcitabine.
Taken
together,
biomaterials
expedite
treatment
facilitating
a
sequential
recognition‐activation
mechanism
suggesting
promising
approach
cell‐mediated
immunotherapy.
Language: Английский
Optimized Design of Hyaluronic Acid–Lipid Conjugate Biomaterial for Augmenting CD44 Recognition of Surface-Engineered NK Cells
Biomacromolecules,
Journal Year:
2024,
Volume and Issue:
25(3), P. 1959 - 1971
Published: Feb. 20, 2024
Triple-negative
breast
cancer
(TNBC)
presents
treatment
challenges
due
to
a
lack
of
detectable
surface
receptors.
Natural
killer
(NK)
cell-based
adaptive
immunotherapy
is
promising
because
the
characteristic
anticancer
effects
killing
malignant
cells
directly
by
secreting
cytokines
and
lytic
granules.
To
maximize
recognition
ability
NK
cells,
biomaterial-mediated
ex
vivo
cell
engineering
has
been
developed
for
sufficient
membrane
immobilization
tumor-targeting
ligands
via
hydrophobic
anchoring.
In
this
study,
we
optimized
amphiphilic
balances
coating
materials
composed
CD44-targeting
hyaluronic
acid
(HA)-poly(ethylene
glycol)
(PEG)-lipid
improve
TNBC
effect.
Changes
in
modular
design
our
material
differentiating
hydrophilic
PEG
length
incorporating
lipid
amount
into
HA
backbones
precisely
regulated
nature
HA-PEG-lipid
conjugates.
The
biomaterial
demonstrated
improved
anchoring
membranes
facilitating
presentation
level
onto
surfaces.
This
led
enhanced
targeting
increasing
formation
immune
synapse,
thereby
augmenting
capability
specifically
toward
CD44-positive
cells.
Our
approach
addresses
solid
tumors
with
deficiency
tumor-specific
antigens
while
offering
valuable
strategy
using
balance
techniques.
Language: Английский
Engineered inulin-based hybrid biomaterials for augmented immunomodulatory responses
Carbohydrate Polymers,
Journal Year:
2024,
Volume and Issue:
340, P. 122311 - 122311
Published: May 23, 2024
Language: Английский
Phenylboronic acid-functionalized biomaterials for improved cancer immunotherapy via sialic acid targeting
Advances in Colloid and Interface Science,
Journal Year:
2024,
Volume and Issue:
333, P. 103301 - 103301
Published: Sept. 6, 2024
Language: Английский
Tailoring tumor-recognizable hyaluronic acid–lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells
Nano Convergence,
Journal Year:
2023,
Volume and Issue:
10(1)
Published: Dec. 14, 2023
Abstract
Natural
killer
(NK)
cells
have
clinical
advantages
in
adoptive
cell
therapy
owing
to
their
inherent
anticancer
efficacy
and
ability
identify
eliminate
malignant
tumors.
However,
insufficient
cancer-targeting
ligands
on
NK
surfaces
often
inhibit
immunotherapeutic
performance,
especially
immunosuppressive
tumor
microenvironment.
To
facilitate
recognition
subsequent
function
of
cells,
we
developed
hyaluronic
acid
(HA,
target
CD44
overexpressed
onto
cancer
cells)-poly(ethylene
glycol)
(PEG,
cytoplasmic
penetration
blocker)-Lipid
(molecular
anchor
for
membrane
decoration
through
hydrophobic
interaction)
conjugates
biomaterial-mediated
ex
vivo
surface
engineering.
Among
these
major
compartments
(i.e.,
Lipid,
PEG
HA),
optimization
lipid
anchors
(in
terms
chemical
structure
intrinsic
amphiphilicity)
is
the
most
important
design
parameter
modulate
interaction
with
dynamic
membranes.
Here,
three
different
types
including
1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine
(C14:0),
1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine
(DSPE,
C18:0),
cholesterol
were
evaluated
maximize
coating
associated
performance
surface-engineered
(HALipid-NK
cells).
Our
results
demonstrated
that
coated
HA-PEG-DSPE
exhibited
significantly
enhanced
efficacies
toward
MDA-MB-231
breast
without
an
off-target
effect
human
fibroblasts
specifically
via
increased
prolonged
duration
HA
surfaces,
thereby
improving
HA-CD44
recognition.
These
suggest
our
HALipid-NK
tumor-recognizable
could
be
further
utilized
various
immunotherapies.
Graphical
Language: Английский
Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 16, 2025
Hepatocellular
carcinoma
stands
as
one
of
the
foremost
contributors
to
cancer-associated
fatalities
globally,
and
limitations
traditional
treatment
methods
have
prompted
researchers
explore
new
therapeutic
options.
Recently,
cell
therapy
has
emerged
a
promising
approach
for
HCC,
showing
significant
potential
in
improving
patient
outcomes.
This
review
article
explores
use
covering
different
types,
mechanisms
behind
their
effectiveness,
recent
advancements
clinical
trials,
ongoing
challenges.
aims
provide
insightful
perspectives
future
research
applications
treating
HCC
by
synthesizing
current
knowledge.
Language: Английский
Ex Vivo Surface Decoration of Phenylboronic Acid onto Natural Killer Cells for Sialic Acid-Mediated Versatile Cancer Cell Targeting
Biomacromolecules,
Journal Year:
2023,
Volume and Issue:
25(1), P. 222 - 237
Published: Dec. 22, 2023
Phenylboronic
acid
(PBA)
has
been
highly
acknowledged
as
a
significant
cancer
recognition
moiety
in
sialic
acid-overexpressing
cells.
In
this
investigation,
lipid-mediated
biomaterial
integrated
PBA
molecules
onto
the
surface
of
natural
killer
(NK)
cells
to
make
receptor-mediated
immune
cell
therapeutic
module.
Therefore,
1,2-distearoyl-sn-glycero-3-phosphorylethanolamine
(DSPE)
lipid-conjugated
di–PEG–PBA
(DSPEPEG-di(PEG–PBA)
was
synthesized.
The
DSPEPEG-di(PEG–PBA)
exhibited
high
affinity
for
(SA),
confirmed
by
fluorescence
spectroscopy
at
pH
6.5
and
7.4.
successfully
anchored
NK
surfaces
(PBA-NK),
maintains
intrinsic
properties
such
viability,
ligand
availability
(FasL
&
TRAIL),
cytokine
secretion
response
LPS.
anticancer
efficacy
PBA-NK
evaluated
against
2D
(MDA-MB-231,
HepG2,
HCT-116)
3D
tumor
spheroids
MDA-MB-231
greatly
enhanced
effects
SA-overexpressing
Thus,
represent
new
strategy
immunotherapy.
Language: Английский
Membrane-immobilized Gemcitabine for Cancer-Targetable NK Cell Surface Engineering
Kyung Mu Noh,
No information about this author
Ashok Kumar Jangid,
No information about this author
Jaewon Park
No information about this author
et al.
Journal of Materials Chemistry B,
Journal Year:
2024,
Volume and Issue:
12(46), P. 12087 - 12102
Published: Jan. 1, 2024
Although
natural
killer
(NK)
cell-based
adoptive
cell
transfer
(ACT)
has
shown
promise
in
cancer
immunotherapy,
its
efficacy
against
solid
tumors
is
limited
the
immunosuppressive
tumor
microenvironment
(TME).
Combinatorial
therapies
involving
chemotherapeutic
drugs
such
as
gemcitabine
(Gem)
and
NK
cells
have
been
developed
to
modulate
TME;
however,
their
clinical
application
constrained
by
low
drug
delivery
efficiency
significant
off-target
toxicity.
In
this
study,
we
membrane-immobilized
Gem
conjugates
(
Language: Английский
Advancements of engineered live oncolytic biotherapeutics (microbe/virus/cells): Preclinical research and clinical progress
Zhengzhuo Qi,
No information about this author
Junmou Gu,
No information about this author
Lihang Qu
No information about this author
et al.
Journal of Controlled Release,
Journal Year:
2024,
Volume and Issue:
375, P. 209 - 235
Published: Sept. 11, 2024
Language: Английский
Networked Cluster Formation via Trigonal Lipid Modules for Augmented Ex Vivo NK Cell Priming
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(3), P. 1556 - 1556
Published: Jan. 26, 2024
Current
cytokine-based
natural
killer
(NK)
cell
priming
techniques
have
exhibited
limitations
such
as
the
deactivation
of
biological
signaling
molecules
and
subsequent
insufficient
maturation
population
during
mass
cultivation
processes.
In
this
study,
we
developed
an
amphiphilic
trigonal
1,2-distearoyl-sn-glycero-3-phosphorylethanolamine
(DSPE)
lipid-polyethylene
glycol
(PEG)
material
to
assemble
NK
clusters
via
multiple
hydrophobic
lipid
insertions
into
cellular
membranes.
Our
conjugate-mediated
ex
vivo
sufficiently
augmented
structural
modulation
clusters,
facilitated
diffusional
signal
exchanges,
finally
activated
with
clusters.
Without
any
inhibition
in
exchanges
intrinsic
proliferative
efficacy
cells,
effectively
prime
produced
increased
interferon-gamma,
especially
early
culture
periods.
conclusion,
present
study
demonstrates
that
our
novel
conjugates
could
serve
a
promising
alternative
for
future
production.
Language: Английский