Abstract
Although
irradiated
induced-pluripotent
stem
cells
(iPSCs)
as
a
prophylactic
cancer
vaccine
elicit
an
antitumor
immune
response,
the
therapeutic
efficacy
of
iPSC-based
vaccines
is
not
promising
due
to
their
insufficient
antigenicity
and
immunosuppressive
tumor
microenvironment.
Here,
we
found
that
neoantigen-engineered
iPSC
can
trigger
neoantigen-specific
T
cell
responses
eradicate
increase
RT
in
poorly
immunogenic
colorectal
(CRC)
triple-negative
breast
(TNBC).
We
generated
neoantigen-augmented
iPSCs
(NA-iPSCs)
by
engineering
AAV2
vector
carrying
murine
neoantigens
evaluated
combination
with
radiotherapy.
After
administration
NA-iPSC
radiotherapy,
~60%
tumor-bearing
mice
achieved
complete
response
microsatellite-stable
CRC
model.
Furthermore,
splenocytes
from
treated
plus
produced
high
levels
IFNγ
secretion
had
greater
cytotoxicity
cells,
suggesting
combined
radiotherapy
elicited
superior
T-cell
cells.
The
NA-iPSCs
engineered
mouse
TNBC
was
also
observed
syngeneic
immunocompetent
risk
spontaneous
lung
liver
metastasis
dramatically
decreased
animal
Altogether,
these
results
indicated
autologous
promote
regression,
reduce
distant
local
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
221(2)
Опубликована: Янв. 16, 2024
Chimeric
antigen
receptor
(CAR)-T
cell
therapies
have
demonstrated
strong
curative
potential
and
become
a
critical
component
in
the
array
of
B-cell
malignancy
treatments.
Successful
deployment
CAR-T
to
treat
hematologic
solid
cancers,
as
well
other
indications
such
autoimmune
diseases,
is
dependent
on
effective
manufacturing
that
impacts
not
only
product
safety
efficacy
but
also
overall
accessibility
patients
need.
In
this
review,
we
discuss
major
process
parameters
autologous
manufacturing,
regulatory
considerations
ongoing
developments
will
enable
next
generation
therapies.
Immunotherapy
can
lead
to
long-term
survival
for
some
cancer
patients,
yet
generalized
success
has
been
hampered
by
insufficient
antigen
presentation
and
exclusion
of
immunogenic
cells
from
the
tumor
microenvironment.
Here,
we
developed
an
approach
reprogram
in
vivo
adenoviral
delivery
transcription
factors
PU.1,
IRF8,
BATF3,
which
enabled
them
present
antigens
as
type
1
conventional
dendritic
cells.
Reprogrammed
remodeled
their
microenvironment,
recruited,
expanded
polyclonal
cytotoxic
T
cells;
induced
regressions;
established
systemic
immunity
multiple
mouse
melanoma
models.
In
human
spheroids
xenografts,
reprogramming
dendritic-like
progressed
independently
immunosuppression,
usually
limits
immunotherapy.
Our
study
paves
way
clinical
trials
immune
cell
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1235 - 1235
Опубликована: Янв. 31, 2025
The
PD1/PD-L1
axis
plays
an
important
immunosuppressive
role
during
the
T-cell-mediated
immune
response,
which
is
essential
for
physiological
homeostasis
of
system.
biology
immunological
microenvironment
extremely
complex
and
crucial
development
treatment
strategies
immunotherapy.
Characterization
immunological,
genomic
or
transcriptomic
landscape
cancer
patients
could
allow
discrimination
between
responders
non-responders
to
anti-PD-1/PD-L1
therapy.
Immune
checkpoint
inhibitor
(ICI)
therapy
has
shown
remarkable
efficacy
in
a
variety
malignancies
landmark
trials
fundamentally
changed
Current
research
focuses
on
maximize
patient
selection
therapy,
clarify
mechanisms
resistance,
improve
existing
biomarkers,
including
PD-L1
expression
tumor
mutational
burden
(TMB),
discover
new
biomarkers.
In
this
review,
we
focus
function
PD-1/PD-L1
signaling
pathway
discuss
genomic,
epigenetic
receiving
Finally,
provide
overview
clinical
testing
antibodies
against
PD-1/PD-L1.
Translational Oncology,
Год журнала:
2023,
Номер
40, С. 101851 - 101851
Опубликована: Дек. 1, 2023
Colorectal
cancer
(CRC)
is
the
third
most
prevalent
in
world.
The
PD-1/PD-L1
pathway
plays
a
crucial
role
modulating
immune
response
to
cancer,
and
PD-L1
expression
has
been
observed
tumor
cells
within
microenvironment
of
CRC.
Thus,
immunotherapy
drugs,
specifically
checkpoint
inhibitors,
have
developed
target
signaling
pathway,
thereby
inhibiting
interaction
between
PD-1
restoring
T-cell
function
cells.
However,
emergence
resistance
mechanisms
can
reduce
efficacy
these
treatments.
To
counter
this,
monoclonal
antibodies
(mAbs)
used
improve
CRC
mAbs
such
as
nivolumab
pembrolizumab
are
currently
approved
for
treatment.
These
impede
receptors,
including
PD-1/PD-L1,
their
combination
therapy
shows
promise
treatment
advanced
This
review
presents
concise
overview
use
blockade
therapeutic
strategy
using
therapies.
Additionally,
this
article
outlines
an
suppressor
well
potential
advantages
administering
inflammatory
agents
Finally,
analyzes
outcomes
clinical
trials
examine
challenges
anti-PD-1/PD-L1
resistance.
Chemical Society Reviews,
Год журнала:
2024,
Номер
53(7), С. 3224 - 3252
Опубликована: Янв. 1, 2024
Neoantigens
play
a
pivotal
role
in
the
field
of
tumour
therapy,
encompassing
stimulation
anti-tumour
immune
response
and
enhancement
targeting
capability.
Nonetheless,
numerous
factors
directly
influence
effectiveness
neoantigens
bolstering
responses,
including
neoantigen
quantity
specificity,
uptake
rates
by
antigen-presenting
cells
(APCs),
residence
duration
within
microenvironment
(TME),
their
ability
to
facilitate
maturation
APCs
for
activation.
Nanotechnology
assumes
significant
several
aspects,
facilitating
release,
promoting
delivery
cells,
augmenting
dendritic
shielding
from
protease
degradation,
optimizing
interactions
between
system.
Consequently,
development
nanotechnology
synergistically
enhances
efficacy
cancer
theranostics.
In
this
review,
we
provide
an
overview
sources,
mechanisms
neoantigen-induced
evolution
precision
neoantigen-based
nanomedicine.
This
encompasses
various
therapeutic
modalities,
such
as
immunotherapy,
phototherapy,
radiotherapy,
chemotherapy,
chemodynamic
other
strategies
tailored
augment
therapeutics.
We
also
discuss
current
challenges
prospects
application
nanomedicine,
aiming
expedite
its
clinical
translation.
Cellular & Molecular Biology Letters,
Год журнала:
2024,
Номер
29(1)
Опубликована: Апрель 12, 2024
Abstract
T
cell
immunity
is
central
to
contemporary
cancer
and
autoimmune
therapies,
encompassing
immune
checkpoint
blockade
adoptive
therapies.
Their
diverse
characteristics
can
be
reprogrammed
by
different
challenges
dependent
on
antigen
stimulation
levels,
metabolic
conditions,
the
degree
of
inflammation.
cell-based
therapeutic
strategies
are
gaining
widespread
adoption
in
oncology
treating
inflammatory
conditions.
Emerging
researches
reveal
that
clustered
regularly
interspaced
palindromic
repeats–associated
protein
9
(CRISPR–Cas9)
genome
editing
has
enabled
cells
more
adaptable
specific
microenvironments,
opening
door
advanced
therapies
preclinical
clinical
trials.
CRISPR–Cas9
edit
both
primary
engineered
cells,
including
CAR-T
TCR-T,
vivo
vitro
regulate
differentiation
activation
states.
This
review
first
provides
a
comprehensive
summary
role
its
applications
studies
for
We
also
explore
application
CRISPR
screen
high-throughput
technology
anticipate
current
limitations
CRISPR–Cas9,
off-target
effects
delivery
challenges,
envisioned
improvements
related
technologies
disease
screening,
diagnosis,
treatment.
