Chimeric
antigen
receptor
(CAR)
T-cell
therapy
shows
unprecedented
efficacy
for
cancer
treatment,
particularly
in
treating
patients
with
various
blood
cancers,
most
notably
B-cell
acute
lymphoblastic
leukemia.
In
recent
years,
CAR
therapies
have
been
investigated
other
hematologic
malignancies
and
solid
tumors.
Despite
the
remarkable
success
of
therapy,
cytokine
release
syndrome
(CRS)
is
an
unexpected
side
effect
that
potentially
life-threatening.
Our
aim
to
reduce
pro-inflammatory
associated
CRS
by
controlling
surface
density
on
T
cells.
We
show
expression
can
be
titrated
primary
cells
using
acoustic-electric
microfluidic
platform.
The
platform
performs
dosage-controlled
delivery
uniformly
mixing
shearing
cells,
delivering
approximately
same
amount
gene
coding
mRNA
into
each
cell.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 4, 2025
Abstract
In
the
past
decades,
Chimeric
Antigen
Receptor
(CAR)-T
cell
therapy
has
achieved
remarkable
success,
leading
to
approval
of
six
therapeutic
products
for
haematological
malignancies.
Recently,
potential
this
also
been
demonstrated
in
non-tumoral
diseases.
Currently,
manufacturing
process
produce
clinical-grade
CAR-T
cells
is
complex,
time-consuming,
and
highly
expensive.
It
involves
multiple
steps,
including
collection
T
from
patients
or
healthy
donors,
vitro
engineering
expansion,
finally
reinfusion
into
patients.
Therefore,
despite
impressive
clinical
outcomes,
ex
vivo
makes
out
reach
many
cancer
Direct
could
be
a
more
rapid
solution
able
circumvent
both
complexity
costs
associated
with
manufactured
cells.
This
novel
approach
allows
completely
eliminate
manipulation
expansion
while
producing
populations
directly
vivo.
To
date,
several
studies
have
feasibility
reprogramming,
by
employing
injectable
viral-
nanocarrier-based
delivery
platforms
tumour
animal
models.
Additionally,
production
might
reduce
incidence,
at
least
severity,
systemic
toxicities
frequently
occurring
produced
cells,
such
as
cytokine
release
syndrome
immune
effector
cell-associated
neurotoxicity
syndrome.
review,
we
highlight
challenges
current
protocols
review
latest
progresses
emerging
field
therapy,
comparing
various
so
far
investigated.
Moreover,
offer
an
overview
advantages
deriving
reprogramming
other
types,
Natural
Killer
macrophages,
CAR
constructs.
Molecular Therapy,
Год журнала:
2024,
Номер
32(8), С. 2711 - 2727
Опубликована: Июнь 27, 2024
Natural
killer
(NK)
cells
eliminate
infected
or
cancer
via
their
cytotoxic
capacity.
NKG2A
is
an
inhibitory
receptor
on
NK
and
often
overexpress
its
ligand
HLA-E
to
evade
cell
surveillance.
Given
the
successes
of
immune
checkpoint
blockade
in
therapy,
interesting
novel
target.
However,
anti-NKG2A
antibodies
have
shown
limited
clinical
response.
In
pursuit
enhancing
cell-mediated
anti-tumor
responses,
we
devised
a
Cas9-based
strategy
delete
KLRC1,
encoding
NKG2A,
human
primary
cells.
Our
approach
involved
electroporation
KLRC1-targeting
Cas9
ribonucleoprotein
resulting
effective
ablation
expression.
Compared
with
antibody
blockade,
Biomaterials,
Год журнала:
2025,
Номер
317, С. 123085 - 123085
Опубликована: Янв. 5, 2025
T
cell
therapy
for
solid
tumors
faces
significant
challenges
due
to
the
immune
off-target
attack
caused
by
loss
of
tumor
surface
antigens
and
inactivation
in
acidic
microenvironment
(TME).
Herein,
we
developed
a
bifunctional
immunomodulator
(MO@NAL)
loading
ovalbumin
(OVA;
model
antigen)
mRNA
(mOVA)
onto
lysozyme-coated
layered
double
hydroxide
nano-aluminum
adjuvant
(NA).
The
NA's
inherent
alkalinity
effectively
neutralizes
excess
acid
within
TME
suppresses
regulatory
cells,
creating
favorable
enhance
cytotoxic
infiltration
activation
tumors.
Particularly,
once
internalization
MO@NAL
efficiently
tags
with
OVA
through
carried
mOVA,
providing
targets
recruiting
directing
antigen-specific
cells
destroy
cells.
In
mice
pre-vaccinated
vaccine,
intratumoral
administration
rapidly
awakens
OVA-specific
memory,
inhibiting
progression
colon
melanoma
at
both
early
advanced
stages.
non-pre-vaccinated
mice,
combining
therapeutic
vaccine
or
adoptive
transfusion
similarly
achieves
robust
suppression.
These
findings
thus
underscore
potential
as
an
effective
safe
enhancing
responses
timely
intervention
progression.
Deleted Journal,
Год журнала:
2025,
Номер
2, С. 1 - 1
Опубликована: Янв. 17, 2025
Messenger
RNA
(mRNA)
technology
has
revolutionized
modern
medicine,
particularly
in
developing
vaccines
and
gene
therapies.
While
its
prominence
soared
during
the
COVID-19
pandemic,
foundation
was
built
on
decades
of
meticulous
research.
This
review
explores
historical
evolution
mRNA
technology,
stabilization
delivery
breakthroughs,
applications
combating
infectious
diseases,
cancer,
genetic
disorders.
The
study
utilized
a
systematic
search
peer-reviewed
articles
from
leading
databases
such
as
PubMed
Scopus,
focusing
advancements
clinical
applications.
Future
potential
treating
chronic
enhancing
immunotherapy,
addressing
public
health
emergencies
is
also
discussed,
emphasizing
need
for
sustained
research
innovation
to
harness
transformative
capabilities
fully.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Авг. 13, 2024
Oral
squamous
cell
carcinoma
(OSCC),
a
major
subtype
of
head
and
neck
cancers,
presents
significant
challenges
due
to
its
aggressive
feature
limited
therapeutic
efficacy
conventional
treatments.
In
response
these
challenges,
Natural
Killer
(NK)
cells,
vital
component
the
innate
immune
system,
are
being
explored
for
their
potential
in
OSCC
inherent
ability
target
eliminate
cancer
cells
without
prior
sensitization.
This
review
uniquely
focuses
on
evolving
role
NK
specifically
OSCC,
incorporating
recent
advancements
CAR-NK
engineering
personalized
therapy
approaches
that
have
not
been
comprehensively
covered
previous
reviews.
The
mechanisms
through
which
exert
cytotoxic
effects
tumor
include
direct
killing
engagement
natural
receptors
antibody-dependent
cellular
cytotoxicity
(ADCC),
making
them
promising
agents
immunotherapy.
Additionally,
article
explores
enhance
antitumor
activity,
such
as
modification
with
chimeric
antigen
(CARs)
specific
antigens.
Clinical
implications
cell-based
therapies,
including
integrating
treatments
existing
protocols
therapy,
examined.
highlights
promise
therapies
improving
outcomes
patients
outlines
future
directions
research
this
dynamic
field
oncological
Vaccines,
Год журнала:
2025,
Номер
13(1), С. 40 - 40
Опубликована: Янв. 6, 2025
Objective:
We
evaluate
the
immunotherapeutic
potential
of
yellow
fever
virus
vaccine
strain
17D
(YFV
17D)
for
intratumoral
therapy
pancreatic
cancer
in
mice.
Methods:
The
cytopathic
effect
YFV
on
mouse
syngeneic
cancers
cells
were
studied
both
vitro
and
vivo
human
vitro.
Results:
demonstrated
a
strong
against
Although
did
not
exhibit
lytic
Pan02
vitro,
single
administration
caused
delay
tumor
growth
an
increase
median
survival
by
30%.
Multiple
injections
further
improve
growth;
however,
it
notably
extended
survival.
Furthermore,
preliminary
immunization
with
enhanced
its
oncotherapeutic
effect.
Conclusions:
Intratumoral
delayed
murine
model
cancer.
fact
that
affected
much
more
strongly
than
appears
promising.
Hence,
we
anticipate
efficacy
YFV-17D-based
oncolytic
will
also
be
higher
carcinomas
compared
to
tumor.
Abstract
Patient‐derived
xenograft
(PDX)
models
provide
a
robust
preclinical
platform
that
preserves
the
genetic
and
phenotypic
heterogeneity
of
patient
tumors
while
mirroring
their
tumor
characteristics,
which
retain
malignant
cells
pathological
structure,
making
them
valuable
for
studying
progression
developing
anticancer
therapies.
This
review
outlines
establishment
PDX
applications
in
research
by
comparing
attributes
limitations
with
other
experimental
models.
It
explores
use
understanding
mechanisms,
resistance
treatment
strategies,
including
radiotherapy,
chemotherapy,
targeted
therapy,
immunotherapy,
nanotherapy,
cell
antibody‐drug
conjugates,
combination
therapy.
Integration
multi‐omics
technologies
is
also
discussed,
along
application
co‐clinical
clinical
studies.
Notably,
this
covers
approximately
30
cancer
types
aims
to
guide
future
research.