The
emergence
of
bispecific
antibodies
has
transformed
cancer
immunotherapy,
highlighting
increased
clinical
efficacy,
especially
in
hematological
malignancies.
These
innovative
molecules
uniquely
target
two
distinct
tumor
antigens
or
separate
epitopes
simultaneously,
demonstrating
potent
antitumor
activity
across
various
cancers.
Despite
their
promise,
challenges
like
rapid
drug
clearance,
off-target
effects,
and
cytokine
release
syndrome
hinder
widespread
therapeutic
application.
Recent
engineering
advancements
antibody
systems
aim
to
overcome
these
challenges,
broadening
coverage.
This
review
offers
insights
into
the
latest
preclinical
progress
outlining
key
faced
by
technique,
exploring
emerging
strategies
address
obstacles.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Июнь 19, 2023
T
cells
are
crucial
for
immune
functions
to
maintain
health
and
prevent
disease.
cell
development
occurs
in
a
stepwise
process
the
thymus
mainly
generates
CD4
Journal of Hematology & Oncology,
Год журнала:
2024,
Номер
17(1)
Опубликована: Июль 27, 2024
Abstract
Cancer
immunotherapies,
represented
by
immune
checkpoint
inhibitors
(ICIs),
have
reshaped
the
treatment
paradigm
for
both
advanced
non-small
cell
lung
cancer
and
small
cancer.
Programmed
death
receptor-1/programmed
receptor
ligand-1
(PD-1/PD-L1)
cytotoxic
T
lymphocyte-associated
antigen-4
(CTLA-4)
are
some
of
most
common
promising
targets
in
ICIs.
Compared
to
ICI
monotherapy,
which
occasionally
demonstrates
resistance
limited
efficacy,
dual
blockade
immunotherapy
targeting
PD-1/PD-L1
CTLA-4
operates
at
different
stages
activation
with
synergistically
enhancing
responses
against
cells.
This
emerging
therapy
heralds
a
new
direction
immunotherapy,
which,
however,
may
increase
risk
drug-related
adverse
reactions
while
improving
efficacy.
Previous
clinical
trials
explored
combination
strategy
anti-PD-1/PD-L1
anti-CTLA-4
agents
cancer,
yet
its
efficacy
remains
be
unclear
inevitable
incidence
immune-related
events.
The
recent
advent
bispecific
antibodies
has
made
this
sort
more
feasible,
aiming
alleviate
toxicity
without
compromising
Thus,
review
highlights
role
treating
further
elucidates
pre-clinical
mechanisms
current
advancements
trials.
Besides,
we
also
provide
novel
insights
into
potential
combinations
therapies
other
strategies
optimize
future
mode
Cancer Biology and Medicine,
Год журнала:
2023,
Номер
20(3), С. 181 - 195
Опубликована: Март 24, 2023
Advances
in
antibody
engineering
have
led
to
the
generation
of
more
innovative
drugs,
such
as
bispecific
antibodies
(bsAbs).
Following
success
associated
with
blinatumomab,
bsAbs
attracted
enormous
interest
field
cancer
immunotherapy.
By
specifically
targeting
two
different
antigens,
reduce
distance
between
tumor
and
immune
cells,
thereby
enhancing
killing
directly.
There
are
several
mechanisms
action
upon
which
been
exploited.
Accumulating
experience
on
checkpoint-based
therapy
has
promoted
clinical
transformation
immunomodulatory
checkpoints.
Cadonilimab
(PD-1
×
CTLA-4)
is
first
approved
bsAb
dual
inhibitory
checkpoints,
confirms
feasibility
In
this
review
we
analyzed
by
checkpoints
their
emerging
applications
Journal of Hematology & Oncology,
Год журнала:
2023,
Номер
16(1)
Опубликована: Май 8, 2023
Abstract
Background
QL1706
(PSB205)
is
a
single
bifunctional
MabPair
(a
novel
technical
platform)
product
consisting
of
two
engineered
monoclonal
antibodies
(anti-PD-1
IgG4
and
anti-CTLA-4
IgG1),
with
shorter
elimination
half-life
(t
1/2
)
for
CTLA-4.
We
report
results
from
phase
I/Ib
study
in
patients
advanced
solid
tumors
who
failed
standard
therapies.
Methods
In
the
I
study,
was
administered
intravenously
once
every
3
weeks
at
one
five
doses
ranging
0.3
to
10
mg/kg,
maximum
tolerated
dose,
recommended
2
dose
(RP2D),
safety,
pharmacokinetics
(PK),
pharmacodynamics
(PD)
were
investigated.
Ib
RP2D
weeks,
preliminary
efficacies
non-small
cell
lung
cancer
(NSCLC),
nasopharyngeal
carcinoma
(NPC),
cervical
(CC),
other
evaluated.
Results
Between
March
2020
July
2021,
518
enrolled
(phase
I,
n
=
99;
Ib,
419).
For
all
patients,
three
most
common
treatment-related
adverse
events
(TRAEs)
rash
(19.7%),
hypothyroidism
(13.5%),
pruritus
(13.3%).
The
TRAEs
immune-related
(irAEs)
grade
≥
occurred
16.0%
8.1%
respectively.
6
10mg/kg
group
experienced
dose-limiting
toxicities
(DLTs)
(grade
thrombocytopenia
4
immune-mediated
nephritis),
so
(MTD)
reached
mg/kg.
determined
be
5
mg/kg
based
on
comprehensive
analysis
tolerability,
PK/PD,
efficacy.
received
RP2D,
objective
response
rate
(ORR)
median
duration
16.9%
(79/468)
11.7
months
(8.3—not
[NR]),
respectively;
ORRs
14.0%
(17/121)
NSCLC,
24.5%
(27/110)
NPC,
27.3%
(15/55)
CC,
7.4%
(2/27)
colorectal
cancer,
23.1%
(6/26)
small
cancer.
immunotherapy-naive
exhibited
promising
antitumor
activities,
especially
24.2%,
38.7%,
28.3%,
Conclusions
well
demonstrated
activity
tumors,
CC
patients.
It
currently
being
evaluated
randomized
II
(NCT05576272,
NCT05179317)
III
(NCT05446883,
NCT05487391)
trials.
Trial
Registration
ClinicalTrials.gov
Identifier:
NCT04296994
NCT05171790.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Март 4, 2024
Immunotherapies
have
revolutionized
the
landscape
of
cancer
treatment.
Regulatory
T
cells
(Tregs),
as
crucial
components
tumor
immune
environment,
has
great
therapeutic
potential.
However,
nonspecific
inhibition
Tregs
in
therapies
may
not
lead
to
enhanced
antitumor
responses,
but
could
also
trigger
autoimmune
reactions
patients,
resulting
intolerable
treatment
side
effects.
Hence,
precision
targeting
and
tumor-infiltrating
is
paramount
importance.
In
this
overview,
we
summarize
characteristics
subpopulations
within
microenvironment
their
inhibitory
mechanisms
responses.
Furthermore,
discuss
current
major
strategies
regulatory
cells,
weighing
advantages
limitations,
representative
clinical
trials
We
believe
that
developing
specifically
target
suppress
holds
promise
for
advancing
immune-based
therapies.
Cell Metabolism,
Год журнала:
2024,
Номер
36(2), С. 229 - 239
Опубликована: Янв. 12, 2024
Tissue
regulatory
T
cells
(Tregs)
exert
pivotal
functions
in
both
immune
and
metabolic
regulation,
maintaining
local
tissue
homeostasis,
integrity,
function.
Accordingly,
Tregs
play
a
crucial
role
controlling
obesity-induced
inflammation
supporting
efficient
muscle
function
repair.
Depending
on
the
context,
are
characterized
by
unique
transcriptomes,
growth,
survival
factors
cell
receptor
(TCR)
repertoires.
This
functional
specialization
offers
potential
to
selectively
target
context-specific
Treg
populations,
tailoring
therapeutic
strategies
specific
niches,
thereby
minimizing
side
effects.
Here,
we
discuss
challenges
perspectives
for
niche-specific
targeting,
which
holds
promise
highly
precise
medical
interventions
combat
disease.
Clinical Pharmacology & Therapeutics,
Год журнала:
2024,
Номер
116(2), С. 315 - 327
Опубликована: Июнь 2, 2024
Bispecific
antibodies,
by
enabling
the
targeting
of
more
than
one
disease-associated
antigen
or
engaging
immune
effector
cells,
have
both
advantages
and
challenges
compared
with
a
combination
two
different
biological
products.
As
December
2023,
there
are
11
U.S.
Food
Drug
Administration-approved
BsAb
products
on
market.
Among
these,
9
been
approved
for
oncology
indications,
8
these
CD3
T-cell
engagers.
Clinical
pharmacology
strategies,
including
dose-related
critical
bispecific
antibody
development.
This
analysis
reviewed
clinical
studies
all
antibodies
in
identified
perspectives
to
support
dose
optimization
regulatory
approvals,
particularly
context
Administration's
Project
Optimus:
(1)
starting
doses
ranges
first-in-human
studies;
(2)
strategies
step-up
full
recommended
phase
2
level(s)
used
registrational
intent;
(3)
restarting
therapy
after
delay;
(4)
considerations
introduction
subcutaneous
doses;
(5)
body
weight
vs.
flat
dosing
strategy;
(6)
management
immunogenicity.
The
learnings
arising
from
this
review
intended
inform
successful
future
