Medical Research Archives,
Год журнала:
2023,
Номер
11(11)
Опубликована: Янв. 1, 2023
The
creation
of
autologous
gene-modified
cell
products,
such
as
CAR-T
cells
(chimeric
antigen
receptor
T
cells)
has
met
with
clinical
success
but
been
severely
restricted
by
cost,
availability,
and
current
commercial
models
central
manufacturing.
Moreover,
the
inability
to
produce
at
reasonable
cost
in
all
largest
centers
slow
innovation.
are
unique
that
these
ex
vivo
expanded
effector
populations
express
activation
receptors
comprised
immunoglobulin-like
binders,
or
other
immune
ligands,
bypassing
restriction
expanding
appropriately
activating
arise
recombination
V-D-J
genetic
elements.
However,
use
a
single
binding
moiety
recognize
leukemia
target
selected
for
generation
escape
mutants,
cryptic
clones
expand
were
not
initially
detected
upon
diagnostic
work-up.
To
meet
this
challenge,
we
have
engineered
both
B
malignancy-specific
HIV
surface
antigen-specific
multiple
moieties,
thereby
reducing
chance
escape.
therapeutic
population
also
requires
complex
set
procedures
includes
procurement
large
number
patient
cells,
most
often
leukapheresis,
using
matrix-associated
antibodies
targeting
an
co-receptor,
gene
vector
permanently
transduce
bioreactor
can
accommodate
expansion
numbers
suitable
infusion.
This
procedures,
combined
processing
model,
led
chain
custody
expensive
temperature-controlled
shipping
requirements.
We
present
here
model
whereby
production
point
care,
simplified
procurement,
purification,
expansion,
reduce
time
expense
generation,
aim
therapies
majority
world,
managed
care
publicly
funded
systems.
produced
point-of-care
ready
process
highly
active,
viable,
preferred
phenotypic
characteristics
associated
efficacy.
Blood Science,
Год журнала:
2023,
Номер
5(4), С. 237 - 248
Опубликована: Окт. 1, 2023
Chimeric
antigen
receptor
(CAR)-T-cell
therapies
have
exhibited
remarkable
efficacy
in
the
treatment
of
hematologic
malignancies,
with
9
CAR-T-cell
products
currently
available.
Furthermore,
CAR-T
cells
shown
promising
potential
for
expanding
their
therapeutic
applications
to
diverse
areas,
including
solid
tumors,
myocardial
fibrosis,
and
autoimmune
infectious
diseases.
Despite
these
advancements,
significant
challenges
pertaining
treatment-related
toxic
reactions
relapses
persist.
Consequently,
current
research
efforts
are
focused
on
addressing
issues
enhance
safety
reduce
relapse
rate.
This
article
provides
a
comprehensive
overview
present
state
therapies,
achievements,
existing
challenges,
future
developments.
Molecular Therapy,
Год журнала:
2024,
Номер
32(4), С. 1000 - 1015
Опубликована: Фев. 27, 2024
Adoptive
cell
therapy
(ACT)
using
T
cells
expressing
chimeric
antigen
receptors
(CARs)
is
an
area
of
intense
investigation
in
the
treatment
malignancies
and
chronic
viral
infections.
One
limitations
ACT-based
CAR
lack
vivo
persistence
maintenance
optimal
function.
Therefore,
alternative
strategies
that
increase
function
CAR-expressing
are
needed.
In
our
studies
humanized
bone
marrow/liver/thymus
(BLT)
mouse
model
nonhuman
primate
(NHP)
HIV
infection,
we
evaluated
two
CAR-based
gene
approaches.
ACT
approach,
used
cytokine
enhancement
preconditioning
to
generate
greater
anti-HIV
Science Translational Medicine,
Год журнала:
2024,
Номер
16(771)
Опубликована: Окт. 30, 2024
Chimeric
antigen
receptor–T
cell
(CAR-T)
therapy
has
transformed
the
management
of
refractory
hematological
malignancies.
Now
that
targeting
pathogenic
cells
interest
with
antigen-directed
cytotoxic
T
lymphocytes
is
possible,
field
expanding
reach
CAR-T
beyond
oncology.
Recently,
breakthrough
progress
been
made
in
application
technology
to
autoimmune
diseases,
exploiting
same
validated
targets
were
used
by
pioneering
therapies
hematology.
Here,
we
discuss
recent
advances
and
outcomes
are
paving
way
for
extension
new
therapeutic
areas,
including
autoimmunity.
Viruses,
Год журнала:
2023,
Номер
15(3), С. 789 - 789
Опубликована: Март 19, 2023
Chimeric
antigen
receptor
(CAR)
technology
is
having
a
huge
impact
in
the
blood
malignancy
field
and
becoming
well-established
therapy
for
many
types
of
leukaemia.
In
recent
decades,
efforts
have
been
made
to
demonstrate
that
CAR-T
cells
potential
as
achieve
sterilizing
cure
human
immunodeficiency
virus
(HIV)
infection.
However,
translation
this
HIV
scenario
has
not
easy,
challenges
appeared
along
way
hinder
consolidation
putative
therapy.
Here,
we
review
origin
development
cells,
describe
advantages
cell
comparison
with
other
therapies,
major
obstacles
currently
faced
regarding
application
field,
specifically,
viral
escape,
infectivity,
accessibility
hidden
reservoirs.
Nonetheless,
promising
results
successfully
tackling
some
these
issues
obtained
clinical
trials
suggest
bright
future
consolidated
Current Opinion in HIV and AIDS,
Год журнала:
2024,
Номер
19(2), С. 62 - 68
Опубликована: Янв. 2, 2024
Purpose
of
review
Despite
decades
insights
about
how
CD8
+
T
cells
and
natural
killer
(NK)
contribute
to
control
infection,
additional
hurdles
(mutational
escape
from
cellular
immunity,
sequence
diversity,
hard-to-access
tissue
reservoirs)
will
need
be
overcome
develop
a
cure.
In
this
review,
we
highlight
recent
findings
novel
mechanisms
antiviral
immunity
discuss
current
strategies
for
therapeutic
deisgn.
Recent
Of
note
are
the
apparent
converging
roles
viral
antigen-specific
MHC-E-restricted
NK
cells,
interleukin
(IL)-15
biologics
boost
cytotoxicity,
broadly
neutralizing
antibodies
in
their
native
form
or
as
anitbody
fragments
neutralize
virus
engage
respectively.
Finally,
renewed
interest
myeloid
relevant
reservoirs
is
an
encouraging
sign
designing
inclusive
strategies.
Summary
Several
studies
have
shown
promise
many
preclinical
models
disease,
including
simian
immunodeficiency
(SIV)/SHIV
infection
nonhuman
primates
HIV
humanized
mice.
However,
each
model
comes
with
its
own
limitations
may
not
fully
predict
human
responses.
We
eagerly
await
results
clinical
trails
assessing
efficacy
these
achieve
reductions
reservoirs,
delay
rebound,
ultimately
elicit
immune
based
without
combination
antiretroviral
therapy
(cART).
Chimeric
antigen
receptor
(CAR)
T
cells
have
made
a
groundbreaking
advancement
in
personalized
immunotherapy
and
achieved
widespread
success
hematological
malignancies.
As
CAR
technology
continues
to
evolve,
numerous
studies
unveiled
its
potential
far
beyond
the
realm
of
oncology.
This
review
focuses
on
current
applications
CAR-based
cellular
platforms
non-neoplastic
indications,
such
as
autoimmune,
infectious,
fibrotic,
senescence-associated
diseases.
Furthermore,
we
delve
into
utilization
CARs
non-T
cell
populations
natural
killer
(NK)
macrophages,
highlighting
their
therapeutic
conditions
offering
for
targeted,
therapies
improve
patient
outcomes
enhanced
quality
life.
Current Opinion in HIV and AIDS,
Год журнала:
2024,
Номер
19(4), С. 169 - 178
Опубликована: Май 1, 2024
Purpose
of
review
Successful
sustained
remission
HIV
infection
has
been
achieved
after
CCR5Δ32/Δ32
allogeneic
hematopoietic
stem
cell
transplantation
for
treatment
leukemia
in
a
small
cohort
people
living
with
(PLWH).
This
breakthrough
demonstrated
that
the
goal
curing
was
achievable.
However,
high
morbidity
and
mortality
associated
bone
marrow
limits
routine
application
this
approach
provides
strong
rationale
pursuing
alternative
strategies
long-term
antiretroviral
therapy
(ART)-free
remission.
Notably,
immune-mediated
control
replication
observed
elite
controllers
posttreatment
suggests
potent
HIV-specific
immune
responses
could
provide
ART-free
PLWH.
The
capacity
chimeric
antigen
receptor
(CAR)-T
cells
engineered
to
target
malignant
induce
cure
cancer
patients
made
an
attractive
PLWH
response.
Here,
we
recent
advances
design
anti-HIV
CAR-T-cell
functional
cure.
Recent
findings
reservoirs
are
established
days
persist
through
clonal
expansion
infected
cells.
continuous
interaction
between
latently
system
shapes
landscape
latency
likely
contributes
viral
controllers.
CAR-T
can
exhibit
superior
antiviral
activity
as
compared
native
T
cells,
particularly
because
they
be
have
multiple
specificities,
resistance
infection,
dual
costimulatory
signaling,
checkpoint
inhibitors,
derivation,
CMV
TCR
coexpression,
tissue
homing
ligands.
These
modifications
significantly
improve
capacities
prevent
escape,
resist
enhance
cytotoxicity,
persistence,
penetration.
Collectively,
these
novel
increased
their
infection.
Summary
Anti-HIV
in-vitro
in-vivo
function.
combination
other
immunotherapeutics
may
contribute
Viruses,
Год журнала:
2024,
Номер
16(10), С. 1588 - 1588
Опубликована: Окт. 9, 2024
Although
combination
antiretroviral
therapy
(ART)
has
been
a
landmark
achievement
for
the
treatment
of
human
immunodeficiency
virus
(HIV),
an
HIV
cure
remained
elusive.
Elimination
latent
reservoirs
that
persist
throughout
infection
is
most
challenging
barrier
to
cure.
The
progressive
marked
by
increasing
size
and
diversity
until
effective
immune
response
mobilized,
which
can
control
but
not
eliminate
infection.
stalemate
between
replication
manifested
establishment
viral
set
point.
ART
initiation
during
early
stage
limits
reservoir
development,
preserves
function,
improves
quality
life,
may
lead
ART-free
remission
in
few
people
living
with
(PLWH).
However,
overwhelming
majority
PLWH,
alone
does
HIV,
lifelong
needed
sustain
suppression.
A
critical
area
research
focused
on
determining
whether
could
be
functionally
cured
if
additional
treatments
are
provided
alongside
ART.
Several
interventions
including
Block
Lock,
Shock
Kill,
broadly
neutralizing
antibody
(bNAb)
therapy,
adoptive
CD8+
T
cell
gene
have
demonstrated
delayed
rebound
and/or
animal
models
some
PLWH.
Whether
or
their
application
improve
success
less
studied.
Herein,
we
review
current
state
clinical
investigative
discuss
potential
likelihood
post-treatment
initiated
