Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(29), P. 6169 - 6173
Published: July 12, 2024
The
chemical
properties
of
disulfides
are
leveraged
in
a
wide
array
applications,
ranging
from
protein-drug
conjugates
for
cancer
treatment
to
self-healing
materials.
However,
disulfide
reduction
strategies
remain
severely
underdeveloped
despite
being
the
key
efficiently
accessing
desired
targets.
Specifically,
no
homogeneous
catalyst
has
been
reported
this
reaction,
and
conditions
that
allow
use
mild
green
reductants
(e.g.,
via
electrochemical
reduction)
not
known.
Herein,
we
unveil
vitamin
B
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(27), P. 5597 - 5601
Published: April 19, 2024
A
traceless
site-selective
conjugation
method,
"AJICAP-M",
was
developed
for
native
antibodies
at
sites
using
Fc-affinity
peptides,
focusing
on
Lys248
or
Lys288.
It
produces
antibody–drug
conjugates
(ADCs)
with
consistent
drug-to-antibody
ratios,
enhanced
stability,
and
simplified
manufacturing.
Comparative
in
vivo
assessment
demonstrated
AJICAP-M's
superior
stability
over
traditional
ADCs.
This
technology
has
been
successfully
applied
to
continuous-flow
manufacturing,
marking
the
first
achievement
ADC
production.
manuscript
outlines
methodology
its
effectiveness
Cancers,
Journal Year:
2024,
Volume and Issue:
16(13), P. 2420 - 2420
Published: June 30, 2024
Antibody-drug
conjugates
(ADCs)
have
been
a
significant
advancement
in
cancer
therapy,
particularly
for
urothelial
(UC).
These
innovative
treatments,
originally
developed
hematological
malignancies,
use
target-specific
monoclonal
antibodies
linked
to
potent
cytotoxic
agents.
This
rational
drug
design
efficiently
delivers
cell-killing
agents
cells
expressing
specific
surface
proteins,
which
are
abundant
UC
owing
their
high
antigen
expression.
is
an
ideal
candidate
ADC
as
it
enhances
on-target
efficacy
while
mitigating
systemic
toxicity.
In
recent
years,
considerable
progress
has
made
understanding
the
biology
and
mechanisms
of
tumor
progression
UC.
However,
despite
introduction
immune
checkpoint
inhibitors,
advanced
characterized
by
rapid
poor
survival
rates.
Targeted
therapies
that
include
anti-nectin
4
enfortumab
vedotin
fibroblast
growth
factor
receptor
inhibitor
erdafitinib.
Enfortumab
shown
prospective
studies
patients
with
UC,
alone
combination
pembrolizumab.
The
anti-Trop-2
sacituzumab
govitecan
also
demonstrated
effectiveness
single-armed
studies.
review
highlights
mechanism
action
ADCs,
application
mono-
therapies,
primary
resistance,
future
perspectives
clinical
treatment.
ADCs
proven
be
increasingly
vital
component
therapeutic
landscape
carcinoma,
filling
gap
treatment
this
progressive
disease.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(13), P. 6969 - 6969
Published: June 26, 2024
Antineoplastic
therapy
is
one
of
the
main
research
themes
this
century.
Modern
approaches
have
been
implemented
to
target
and
heighten
effect
cytostatic
drugs
on
tumors
diminish
their
general/unspecific
toxicity.
In
context,
antibody-drug
conjugates
(ADCs)
represent
a
promising
successful
strategy.
The
aim
review
was
assess
different
aspects
regarding
ADCs.
They
were
presented
from
chemical
pharmacological
perspective
like
structure,
conjugation
development
particularities
alongside
effects,
clinical
trials,
safety
issues
perspectives
challenges
for
future
use
these
discussed.
Representative
examples
include
but
are
not
limited
following
structural
components
ADCs:
monoclonal
antibodies
(trastuzumab,
brentuximab),
linkers
(pH-sensitive,
reduction-sensitive,
peptide-based,
phosphate-based,
others),
payloads
(doxorubicin,
emtansine,
ravtansine,
calicheamicin).
Regarding
pharmacotherapy
success,
high
effectiveness
expectation
associated
with
ADC
treatment
supported
by
large
number
ongoing
trials.
Major
such
as
strategies
first
discussed,
advantages
disadvantages,
efficacy,
offering
retrospective
insight
subject.
second
part
prospective,
focusing
various
plans
overcome
previously
identified
difficulties.
International Journal of Nanomedicine,
Journal Year:
2025,
Volume and Issue:
Volume 20, P. 723 - 739
Published: Jan. 1, 2025
None
of
the
antibody-drug
conjugates
(ADCs)
targeting
Claudin
18.2
(CLDN18.2)
have
received
approval
from
regulatory
authorities
due
to
their
limited
clinical
benefits.
Leveraging
radiosensitizing
ability
Deruxtecan
(DXd)
and
internal
radiation
therapy
131I
for
tumors,
we
aimed
develop
first
radio-antibody-drug
(RADCs)
treatment
gastric
cancer.
The
CLDN18.2-specific
antibody
HLX58
was
conjugated
with
payload
DXd
through
a
cleavable
maleimide
glycynglycyn-phenylalanyn-glycyn
(GGFG)
peptide
linker.
HLX58-Der
labeled
produce
RADC-131I-HLX58-Der.
125I
imaging
CLDN18.2-positive
providing
reference
RADC
in
solid
tumors.
antigen-binding
properties
biodistribution
were
studied
both
vitro
vivo.
cytotoxic
effects
evaluated
tumor
cell
lines
xenografts.
successfully
using
GGFG
linker
Both
125I-HLX58
131I-HLX58-Der
exhibited
significant
binding
affinity
cancer
line.
effect
observed
line,
an
IC50
11.28
ng/mL.
In
terms
cytotoxicity,
greater
activity
compared
HLX58-Der.
demonstrated
similar
profiles
models,
achieving
5.72
±
0.41%ID/g
(48
h)
5.83
(72
tissues
postinjection,
respectively.
average
size
groups
treated
reduced
by
factors
12.15
4.80,
respectively,
control
group.
no
toxic
on
hepatorenal
function,
routine
blood
tests,
or
major
organs
mice
when
These
findings
validate
potential
RADCs
CLDN18.2
treating
CLDN18.2-expressing
Antibody Therapeutics,
Journal Year:
2025,
Volume and Issue:
8(1), P. 68 - 85
Published: Jan. 1, 2025
Abstract
Photoimmunotherapy
(PIT)
involves
the
targeted
delivery
of
a
photosensitizer
through
antibody
conjugation,
which,
upon
binding
to
its
cellular
target
and
activation
by
external
irradiation,
induces
localized
toxicity.
This
approach
addresses
several
limitations
conventional
cancer
therapies,
such
as
chemo-
radiotherapies,
which
result
in
off-target
effects
that
significantly
reduce
patient
quality
life.
Furthermore,
PIT
improves
on
challenges
encountered
with
photodynamic
therapy
(PDT),
nonspecific
localization
photosensitizer,
often
results
unintended
toxicities.
Although
was
first
proposed
early
1980s,
clinical
applications
have
been
constrained
engineering,
conjugation
chemistries,
optical
technologies.
However,
recent
advances
antibody–drug
conjugate
(ADC)
research
emergence
sophisticated
laser
technologies
greatly
benefited
broader
applicability
PIT.
Notably,
near-infrared
photoimmunotherapy
(NIR-PIT)
treatment
for
head
neck
has
approved
Japan
is
currently
phase
III
trials
USA.
A
significant
advantage
over
traditional
ADCs
management
agnostic
nature
PDT,
making
it
more
adaptable
different
tumor
types.
Specifically,
can
act
stem
cells
displaying
resistance
aggressive
phenotypes—a
capability
beyond
scope
alone.
review
provides
an
overview
mechanism
action
NIR-PIT,
highlighting
adaptability
application
therapeutics,
concludes
exploring
potential
advancing
treatments.
