Mirvetuximab Soravtansine Induces Potent Cytotoxicity and Bystander Effect in Cisplatin-Resistant Germ Cell Tumor Cells
Cells,
Год журнала:
2025,
Номер
14(4), С. 287 - 287
Опубликована: Фев. 15, 2025
Patients
with
treatment-refractory/relapsing
germ
cell
tumors
(GCTs)
have
a
dismal
prognosis
due
to
lack
of
any
effective
therapy.
Moreover,
the
efficacy
newly
approved
targeted
therapies
remains
unexplored
for
cisplatin-resistant
GCTs.
Previously,
it
was
demonstrated
that
folate
receptor
α
(FRα)
is
overexpressed
in
many
tumor
types
and
efficiently
by
antibody-drug
conjugate
(ADC)
mirvetuximab
soravtansine
(MIRV)
cancers.
We
hypothesized
FRα
represents
an
attractive
target
treating
treatment-refractory
determined
expression
FOLR1
gene
broad
range
GCT
lines
xenografts.
tested
antitumor
MIRV
on
cells
vitro
explored
ability
treatment
induce
bystander
effect
direct
coculture
FRα-high
FRα-low
cells.
found
has
significantly
higher
testicular
GCTs
(TGCTs)
than
normal
tissue.
highly
expressed
TCam2,
JEG3,
JAR,
NOY1
their
respective
variants.
induced
apoptosis
potent
antiproliferative
adherent
3D
spheroid
cultures
vitro.
A
significant
decrease
2102EP_R_NL
observed
presence
NOY1_R_SK
12.5
nM
MIRV,
showing
coculture.
Immunohistochemical
analysis
confirmed
Folr1
protein
patients
TGCTs
postchemotherapy
chemo-naïve
patients,
as
well
unfavorable
prognosis.
In
this
study,
we
present
data
suggesting
(T)GCT
vivo,
anti-FRα-targeting
should
be
investigated
modality
subset
TGCTs.
effects,
thus
its
potential
further
preclinical
exploration
drug
repurposing
salvage
regime
refractory
disease.
Язык: Английский
Immunoconjugates as an Efficient Platform for Drug Delivery: A Resurgence of Natural Products in Targeted Antitumor Therapy
Pharmaceuticals,
Год журнала:
2024,
Номер
17(12), С. 1701 - 1701
Опубликована: Дек. 17, 2024
The
present
review
provides
a
detailed
and
comprehensive
discussion
on
antibody–drug
conjugates
(ADCs)
as
an
evolving
new
modality
in
the
current
therapeutic
landscape
of
malignant
diseases.
principle
concepts
targeted
delivery
highly
toxic
agents
forsaken
stand-alone
drugs
are
examined
detail,
along
with
biochemical
technological
tools
for
their
successful
implementation.
An
extensive
analysis
ADCs’
major
components
is
conducted
parallel
function
impact
stability,
efficacy,
safety,
resistance
profiles
immunoconjugates.
scope
article
covers
classes
currently
validated
natural
compounds
used
payloads,
emphasis
structural
mechanistic
features,
origin,
distribution.
Future
perspectives
design
thoroughly
explored,
addressing
inherent
or
emerging
challenges
limitations.
survey
also
overview
molecular
rationale
active
tumor
targeting
ADC-based
platforms,
exploring
cellular
biology
clinical
relevance
markers
“homing”
mechanism
both
hematological
solid
malignancies.
Язык: Английский