Cytotherapy,
Journal Year:
2023,
Volume and Issue:
25(6), P. 670 - 682
Published: Feb. 26, 2023
Chimeric
antigen
receptor
(CAR)
T
cells
have
demonstrated
remarkable
efficacy
against
hematological
malignancies;
however,
they
not
experienced
the
same
success
solid
tumors
such
as
glioblastoma
(GBM).
There
is
a
growing
need
for
high-throughput
functional
screening
platforms
to
measure
CAR
T-cell
potency
tumor
cells.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: June 9, 2022
Adoptive
transfer
of
chimeric
antigen
receptor
(CAR)
T
lymphocytes
is
a
powerful
technology
that
has
revolutionized
the
way
we
conceive
immunotherapy.
The
impressive
clinical
results
complete
and
prolonged
response
in
refractory
relapsed
diseases
have
shifted
landscape
treatment
for
hematological
malignancies,
particularly
those
lymphoid
origin,
opens
up
new
possibilities
solid
neoplasms.
However,
widening
use
cell
therapy
hampered
by
accessibility
to
viral
vectors
are
commonly
used
transfection.
In
era
messenger
RNA
(mRNA)
vaccines
CRISPR/Cas
(clustered
regularly
interspaced
short
palindromic
repeat–CRISPR-associated)
precise
genome
editing,
novel
virus-free
methods
engineering
emerging
as
more
versatile,
flexible,
sustainable
alternative
next-generation
CAR
manufacturing.
Here,
discuss
how
non-viral
can
address
some
limitations
gene
allow
us
deliver
genetic
information
stable,
effective
straightforward
manner.
particular,
main
transposon
systems
such
Sleeping
Beauty
(SB)
piggyBac
(PB),
utilization
mRNA,
innovative
approaches
nanotechnology
like
Lipid-based
Polymer-based
DNA
nanocarriers
nanovectors.
We
also
describe
most
relevant
preclinical
data
recently
led
trials,
related
safety
efficacy
aspects.
will
provide
practical
considerations
future
trials
enable
successful
safe
with
generation.
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.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: March 15, 2024
Disialoganglioside
GD2
is
a
promising
target
for
immunotherapy
with
expression
primarily
restricted
to
neuroectodermal
and
epithelial
tumor
cells.
Although
its
role
in
the
maintenance
repair
of
neural
tissue
well-established,
functions
during
normal
organism
development
remain
understudied.
Meanwhile,
studies
have
shown
that
plays
an
important
tumorigenesis.
Its
include
proliferation,
invasion,
motility,
metastasis,
high
ability
transform
microenvironment
may
be
associated
malignant
phenotype.
Structurally,
glycosphingolipid
stably
expressed
on
surface
cells,
making
it
suitable
candidate
targeting
by
antibodies
or
chimeric
antigen
receptors.
Based
mouse
monoclonal
antibodies,
humanized
their
combinations
cytokines,
toxins,
drugs,
radionuclides,
nanoparticles
as
well
receptor
been
developed.
Furthermore,
vaccines
photoimmunotherapy
are
being
used
treat
GD2-positive
tumors,
aptamers
can
targeting.
In
field
cell
therapy,
allogeneic
immunocompetent
cells
also
utilized
enhance
therapy.
Efforts
currently
made
optimize
modifying
design
transducing
not
only
αβ
T
but
γδ
NK
NKT
macrophages.
addition,
combine
both
diagnostic
therapeutic
methods,
allowing
early
detection
disease
minimal
residual
disease.
This
review
discusses
each
method
strategy,
advantages
disadvantages,
highlights
future
directions
Molecular Cancer,
Journal Year:
2023,
Volume and Issue:
22(1)
Published: May 6, 2023
Abstract
Chimeric
antigen
receptor
(CAR)
T-cell
therapy
has
made
remarkable
progress
in
cancer
immunotherapy,
but
several
challenges
with
unclear
mechanisms
hinder
its
wide
clinical
application.
Single-cell
sequencing
technologies,
the
powerful
unbiased
analysis
of
cellular
heterogeneity
and
molecular
patterns
at
unprecedented
resolution,
have
greatly
advanced
our
understanding
immunology
oncology.
In
this
review,
we
summarize
recent
applications
single-cell
technologies
CAR
therapy,
including
biological
characteristics,
latest
response
adverse
events,
promising
strategies
that
contribute
to
development
target
selection.
Generally,
propose
a
multi-omics
research
mode
guide
potential
future
on
therapy.
Molecular Cancer,
Journal Year:
2023,
Volume and Issue:
22(1)
Published: June 26, 2023
Abstract
Background
Chimeric
Antigen
Receptor
(CAR)
T
cells
are
now
standard
of
care
(SOC)
for
some
patients
with
B
cell
and
plasma
malignancies
could
disrupt
the
therapeutic
landscape
solid
tumors.
However,
access
to
CAR-T
is
not
adequate
meet
clinical
needs,
in
part
due
high
cost
long
lead
times
manufacturing
grade
virus.
Non-viral
site
directed
CAR
integration
can
be
accomplished
using
CRISPR/Cas9
double-stranded
DNA
(dsDNA)
or
single-stranded
(ssDNA)
via
homology-directed
repair
(HDR),
however
yields
this
approach
have
been
limiting
application
large
sufficient
demands
outside
early
phase
trials
limited
(ssDNA).
Methods
We
applied
homology-independent
targeted
insertion
(HITI)
HDR
nanoplasmid
insert
an
anti-GD2
into
receptor
alpha
constant
(TRAC)
locus
compared
both
strategies
our
system.
Next,
we
optimized
post-HITI
CRISPR
EnrichMENT
(CEMENT)
seamlessly
integrate
it
a
14-day
process
knock-in
viral
transduced
cells.
Finally,
explored
off-target
genomic
toxicity
engineering
approach.
Results
Here,
show
that
utilizing
delivered
HITI
provides
highly
functional
CEMENT
enriched
approximately
80%
purity,
resulting
therapeutically
relevant
dose
ranges
5.5
×
10
8
–3.6
9
+
were
functionally
comparable
did
any
evidence
toxicity.
Conclusions
Our
work
novel
platform
perform
guided
primary
human
T-cells
holds
potential
increase
therapies.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(1), P. 119 - 119
Published: Jan. 6, 2024
T
lymphocytes
represent
a
promising
target
for
genome
editing.
They
are
primarily
modified
to
recognize
and
kill
tumor
cells
or
withstand
HIV
infection.
In
most
studies,
cell
editing
is
performed
using
the
CRISPR/Cas
technology.
Although
this
technology
easily
programmable
widely
accessible,
its
efficiency
of
was
initially
low.
Several
crucial
improvements
were
made
in
components
their
delivery
methods,
as
well
culturing
conditions
cells,
before
reasonable
level
suitable
clinical
applications
achieved.
review,
we
summarize
describe
aforementioned
parameters
that
affect
human
technology,
with
special
focus
on
gene
knock-in.
Molecular Therapy — Methods & Clinical Development,
Journal Year:
2024,
Volume and Issue:
32(2), P. 101249 - 101249
Published: April 10, 2024
Manufacturing
chimeric
antigen
receptor
(CAR)
T
cell
therapies
is
complex,
with
limited
understanding
of
how
medium
composition
impacts
phenotypes.
CRISPR-Cas9
ribonucleoproteins
can
precisely
insert
a
CAR
sequence
while
disrupting
the
endogenous
alpha
constant
(
Journal of Translational Medicine,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: May 30, 2024
Abstract
Target
cancer
therapy
has
been
developed
for
clinical
treatment
based
on
the
discovery
of
CRISPR
(clustered
regularly
interspaced
short
palindromic
repeat)
-Cas
system.
This
forefront
and
cutting-edge
scientific
technique
improves
research
into
molecular
level
is
currently
widely
utilized
in
genetic
investigation
precision
therapy.
In
this
review,
we
summarized
modification
by
CRISPR/Cas
screening
system,
discussed
key
components
successful
screening,
including
Cas
enzymes,
guide
RNA
(gRNA)
libraries,
target
cells
or
organs.
Furthermore,
focused
application
CAR-T
cell
therapy,
drug
target,
selection
both
ex
vivo
with
addition,
elucidated
advantages
potential
obstacles
system
medicine
described
prospects
future
summary,
provide
a
comprehensive
practical
perspective
development
defects,
aiming
to
further
improve
accuracy
individualized
gene