A
cell-surface
ectonucleotidase
CD39
mediates
the
conversion
of
extracellular
ATP
into
immunosuppressive
adenosine
with
another
CD73.
The
elevated
in
tumor
microenvironment
(TME)
attenuates
antitumor
immunity,
which
promotes
cell
immunologic
escape
and
progression.
Anti-CD39
monoclonal
antibodies
(mAbs),
suppress
enzymatic
activity,
can
be
applied
to
therapy.
Therefore,
an
understanding
relationship
between
inhibitory
activity
epitope
mAbs
is
important.
We
previously
established
anti-mouse
(mCD39)
mAb,
C39Mab-1
using
Cell-Based
Immunization
Screening
(CBIS)
method.
In
this
study,
we
determined
critical
flow
cytometry.
performed
PA
tag
(12
amino
acids)-substituted
analysis
(named
scanning)
RIEDL
(5
determine
By
combination
scanning
scanning,
identified
conformational
epitope,
spanning
three
segments
275th
279th,
282nd
291st,
306th
323rd
acids
mCD39.
These
analyses
would
contribute
identification
membrane
proteins.
CD44
is
a
type
I
transmembrane
glycoprotein
associated
with
poor
prognosis
in
various
solid
tumors.
Since
plays
critical
role
tumor
development
by
regulating
cell
adhesion,
survival,
proliferation
and
stemness,
it
has
been
considered
target
for
therapy.
Anti‑CD44
monoclonal
antibodies
(mAbs)
have
developed
applied
to
antibody‑drug
conjugates
chimeric
antigen
receptor‑T
Anti-pan‑CD44
mAbs,
C44Mab‑5
C44Mab‑46,
which
recognize
both
standard
(CD44s)
variant
isoforms
were
previously
developed.
The
present
study
generated
mouse
IgG2a
version
of
the
anti‑pan‑CD44
mAbs
(5‑mG2a
C44Mab‑46‑mG2a)
evaluate
antitumor
activities
against
CD44‑positive
cells.
Both
5‑mG2a
C44Mab‑46‑mG2a
recognized
CD44s‑overexpressed
CHO‑K1
(CHO/CD44s)
cells
esophageal
line
(KYSE770)
flow
cytometry.
Furthermore,
could
activate
effector
presence
CHO/CD44s
exhibited
complement-dependent
cytotoxicity
KYSE770
administration
significantly
suppressed
xenograft
compared
control
IgG2a.
These
results
indicate
that
exert
cancers
be
promising
therapeutic
regimen
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy,
Год журнала:
2024,
Номер
43(2), С. 44 - 52
Опубликована: Март 20, 2024
A
cell-surface
ectonucleotidase
CD39
mediates
the
conversion
of
extracellular
adenosine
triphosphate
into
immunosuppressive
with
another
CD73.
The
elevated
in
tumor
microenvironment
attenuates
antitumor
immunity,
which
promotes
cell
immunologic
escape
and
progression.
Anti-CD39
monoclonal
antibodies
(mAbs),
suppress
enzymatic
activity,
can
be
applied
to
therapy.
Therefore,
an
understanding
relationship
between
inhibitory
activity
epitope
mAbs
is
important.
We
previously
established
anti-mouse
(anti-mCD39)
mAb,
C
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9190 - 9190
Опубликована: Авг. 24, 2024
CD44
regulates
cell
adhesion,
proliferation,
survival,
and
stemness
has
been
considered
a
tumor
therapy
target.
possesses
the
shortest
standard
(CD44s)
variety
of
variant
(CD44v)
isoforms.
Since
expression
CD44v
is
restricted
in
epithelial
cells
carcinomas
compared
to
CD44s,
promising
target
for
monoclonal
antibody
(mAb)
therapy.
We
previously
developed
an
anti-CD44v10
mAb,
C
Current Issues in Molecular Biology,
Год журнала:
2023,
Номер
45(7), С. 5248 - 5262
Опубликована: Июнь 21, 2023
Head
and
neck
squamous
cell
carcinoma
(HNSCC)
is
the
most
common
type
of
head
cancer,
has
been
revealed
as
second-highest
expression
CD44
in
cancers.
investigated
a
cancer
stem
marker
HNSCC
plays
critical
role
tumor
malignant
progression.
Especially,
splicing
variant
isoforms
(CD44v)
are
overexpressed
cancers
considered
promising
target
for
diagnosis
therapy.
We
developed
monoclonal
antibodies
(mAbs)
against
by
immunizing
mice
with
CD44v3–10-overexpressed
PANC-1
cells.
Among
established
clones,
C44Mab-18
(IgM,
kappa)
reacted
CHO/CD44v3–10,
but
not
CHO/CD44s
parental
CHO-K1
using
flow
cytometry.
The
epitope
mapping
peptides
that
cover
exon-encoded
regions
recognized
border
sequence
between
10
constant
exon
16-encoded
sequence.
These
results
suggest
recognizes
10-containing
CD44v,
CD44s.
Furthermore,
could
recognize
human
oral
(OSCC)
line,
HSC-3,
apparent
dissociation
(KD)
CHO/CD44v3–10
HSC-3
was
1.6
×
10−7
M
1.7
M,
respectively.
detected
CD44v3–10
Western
blotting,
endogenous
CD44v10
immunohistochemistry
OSCC
tissues.
indicate
useful
detecting
cytometry
immunohistochemistry.
Antibodies,
Год журнала:
2023,
Номер
12(3), С. 42 - 42
Опубликована: Июнь 21, 2023
Epidermal
Growth
Factor
Receptor
(EGFR)
overexpression
or
its
mutation
mediates
the
sustaining
proliferative
signaling,
which
is
an
important
hallmark
of
cancer.
Human
EGFR-targeting
monoclonal
antibody
(mAb)
therapy
such
as
cetuximab
has
been
approved
for
clinical
use
in
patients
with
colorectal
cancers
and
head
neck
squamous
cell
carcinomas.
A
reliable
preclinical
mouse
model
essential
to
further
develop
mAb
against
EGFR.
Therefore,
sensitive
mAbs
EGFR
(mEGFR)
should
be
established.
In
this
study,
we
developed
a
specific
mEGFR
using
Cell-Based
Immunization
Screening
(CBIS)
method.
The
established
anti-mEGFR
mAb,
EMab-300
(rat
IgG1,
kappa),
reacted
mEGFR-overexpressed
Chinese
hamster
ovary-K1
(CHO/mEGFR)
endogenously
mEGFR-expressed
lines,
including
NMuMG
(a
mammary
gland
epithelial
cell)
Lewis
lung
carcinoma
cells,
flow
cytometry.
kinetic
analysis
cytometry
indicated
that
KD
CHO/mEGFR
was
4.3
×
10-8
M
1.9
M,
respectively.
These
results
applies
detection
may
useful
obtain
proof
concept
studies.
Antibodies,
Год журнала:
2023,
Номер
12(3), С. 45 - 45
Опубликована: Июль 4, 2023
Gastric
cancer
(GC)
is
the
third
leading
cause
of
cancer-related
deaths
worldwide.
GC
with
peritoneal
metastasis
exhibits
a
poor
prognosis
due
to
lack
effective
therapy.
A
comprehensive
analysis
malignant
ascites
identified
genomic
alterations
and
significant
amplifications
driver
genes,
including
CD44.
CD44
its
splicing
variants
are
overexpressed
in
tumors,
play
crucial
roles
acquisition
invasiveness,
stemness,
resistance
treatments.
Therefore,
development
CD44-targeted
monoclonal
antibodies
(mAbs)
important
for
diagnosis
In
this
study,
we
immunized
mice
CD44v3-10-overexpressed
PANC-1
cells
established
several
dozens
clones
that
produce
anti-CD44v3-10
mAbs.
One
(C44Mab-94;
IgG1,
kappa)
recognized
variant-8-encoded
region
peptide,
indicating
C44Mab-94
specific
mAb
CD44v8.
Furthermore,
could
recognize
CHO/CD44v3-10
cells,
oral
squamous
cell
carcinoma
line
(HSC-3),
or
lines
(MKN45
NUGC-4)
flow
cytometric
analyses.
detect
exogenous
CD44v3-10
endogenous
CD44v8
western
blotting
stained
formalin-fixed
paraffin-embedded
gastric
cells.
These
results
indicate
useful
detecting
variety
experimental
methods
expected
become
usefully
applied
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 4, 2024
Type
1
diabetes
(T1D)
arises
from
autoimmune-mediated
destruction
of
insulin-producing
pancreatic
beta
cells.
Recent
advancements
in
the
technology
generating
cells
human
pluripotent
stem
(SC-beta
cells)
have
facilitated
exploration
cell
replacement
therapies
for
treating
T1D.
However,
persistent
threat
autoimmunity
poses
a
significant
challenge
to
survival
transplanted
SC-beta
Genetic
engineering
is
promising
approach
enhance
immune
resistance
as
we
previously
showed
by
inactivating
Renalase
(Rnls)
gene.
Here,
demonstrate
that
Rnls
loss
function
shapes
mediating
regulatory
natural
killer
(NK)
phenotype
important
induction
tolerogenic
antigen-presenting
Rnls-deficient
mediate
cell-cell
contact-independent
hallmark
anti-inflammatory
cytokine
Tgfβ1
NK
In
addition,
surface
expression
checkpoints
CD47
and
Ceacam1
markedly
elevated
on
deficient
Rnls.
Altered
glucose
metabolism
mutant
involved
upregulation
expression.
These
findings
are
crucial
better
understand
how
genetically
engineered
shape
autoimmunity,
giving
valuable
insights
future
therapeutic
treat
cure
Cancer Science,
Год журнала:
2023,
Номер
114(10), С. 3972 - 3983
Опубликована: Авг. 22, 2023
Carcinoma
cells
possess
high
proliferative
and
invasive
potentials
exhibit
a
resilience
against
stresses,
metabolic
disorder,
therapeutic
efforts.
These
properties
are
mainly
acquired
by
genetic
alterations
including
driver
gene
mutations.
However,
the
detailed
molecular
mechanisms
have
not
been
fully
elucidated.
Here,
we
provide
novel
mechanism
connecting
oncogenic
signaling
tumorigenic
transforming
growth
factor-β1-stimulated
clone
22
(TSC-22)
family
protein,
THG-1
(also
called
as
TSC22D4).
is
localized
at
basal
layer
of
normal
squamous
epithelium
overexpressed
in
cell
carcinomas
(SCCs).
knockdown
suppressed
SCC
proliferation,
invasiveness,
xenograft
tumor
formation.
In
contrast,
overexpression
promoted
EGF-induced
proliferation
stratified
Furthermore,
phosphorylated
receptor
tyrosine
kinase
(RTK)-RAS-ERK
pathway,
which
oncogene-mediated
tumorigenesis.
Moreover,
involves
alternative
splicing
CD44
variants,
regulator
stemness,
oxidative
stress
resistance
under
RTK
pathway.
findings
highlight
pivotal
roles
effector
tumorigenesis,
detection
phosphorylation
our
established
specific
antibody
could
contribute
to
cancer
diagnosis
therapy.
The
Epidermal
Growth
Factor
Receptor
(EGFR)
overexpression
or
its
mutation
mediates
the
sustaining
proliferative
signaling
in
cancers.
Human
EGFR-targeting
monoclonal
antibody
(mAb)
therapy
such
as
cetuximab
has
been
approved
for
clinical
use
patients
with
colorectal
cancers
and
head
neck
squamous
cell
carcinomas.
A
reliable
preclinical
mouse
model
is
essential
to
further
develop
mAb
against
EGFR.
However,
a
EGFR
(mEGFR)
flow
cytometry
not
established.
In
this
study,
we
developed
specific
sensitive
mEGFR
using
Cell-Based
Immunization
Screening
(CBIS)
method.
established
anti-mEGFR
mAb,
EMab-300
(rat
IgG1,
kappa)
reacted
mEGFR-overexpressed
Chinese
hamster
ovary-K1
(CHO/mEGFR)
endogenously
mEGFR-expressed
lines,
including
NMuMG
(a
mammary
gland
epithelial
cell)
Lewis
lung
carcinoma
cells
by
cytometry.
kinetic
analysis
indicated
that
dissociation
constant
(KD)
of
CHO/mEGFR
was
4.3
×
10−8
M
1.9
M,
respectively.
These
results
applies
detection
cytometry,
expected
study.
