Microbes Saving Lives and Reducing Suffering
Microbial Biotechnology,
Год журнала:
2025,
Номер
18(1)
Опубликована: Янв. 1, 2025
Язык: Английский
Plasticity of BioPhi-Driven Humanness Optimization in ScFv-CD99 Binding Affinity Validated Through AlphaFold, HADDOCK, and MD Simulations
Kanokporn Sornsuwan,
Thanathat Pamonsupornwichit,
On-anong Juntit
и другие.
Computational and Structural Biotechnology Journal,
Год журнала:
2025,
Номер
27, С. 369 - 382
Опубликована: Янв. 1, 2025
BioPhi-guided
humanization
was
utilized
to
enhance
the
humanness
of
a
humanized
single-chain
variable
fragment
targeting
CD99,
leading
development
two
variants:
HuScFvMT99/3BP
and
HuScFvMT99/3HY.
The
variant
incorporated
framework
region
modifications,
modest
improvements
in
humanness,
particularly
VH
domain,
although
VL
domain
remained
suboptimal.
To
address
this
limitation,
HuScFvMT99/3HY
designed
by
combining
wild-type
with
HuScFvMT99/3BP.
Molecular
dynamics
simulations
employing
AlphaFold2,
AlphaFold3,
HADDOCK
were
performed
evaluate
HuScFv-CD99
peptide
complexes.
AF2-based
demonstrated
enhanced
binding
free
energy
(ΔGbinding)
for
both
variants
compared
HuScFvMT99/3WT.
However,
ΔGbinding
values
obtained
from
AF3
HD
inconsistent,
exhibiting
weakest
affinity.
While
patterns
derived
AlphaFold3
aligned,
amino
acid
decomposition
analysis
revealed
variations
interaction
coordinates
predicted
Root-mean-square
deviation
indicated
improved
structural
stability
(0.975
Å)
(1.075
relative
HuScFvMT99/3WT
(1.225
Å).
Biolayer
interferometry
further
confirmed
that
exhibited
highest
affinity
(KD
=
1.35
×
10⁻⁷
M)
2.64
3.95
M).
Supporting
evidence
provided
ELISA
flow
cytometry
experiments.
PITHA
high
immunogenicity
risk
all
variants,
despite
displaying
larger
complementarity-determining
(CDR)
cavity,
more
hydrophobic
CDR-H3
loop.
These
findings
highlight
delicate
balance
between
enhancing
preserving
functional
integrity
critical
therapeutic
antibody
development.
Язык: Английский
Antitumor Activities of a Humanized Cancer-Specific Anti-HER2 Monoclonal Antibody, humH2Mab-250 in Human Breast Cancer Xenografts
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1079 - 1079
Опубликована: Янв. 26, 2025
Monoclonal
antibody
(mAb)
and
cell-based
immunotherapies
represent
cutting-edge
strategies
for
cancer
treatment.
However,
safety
concerns
persist
due
to
the
potential
targeting
of
normal
cells
that
express
reactive
antigens.
Therefore,
it
is
crucial
develop
cancer-specific
mAbs
(CasMabs)
can
bind
antigens
exhibit
antitumor
activity
in
vivo,
thereby
reducing
risk
adverse
effects.
We
previously
screened
human
epidermal
growth
factor
receptor
2
(HER2)
successfully
developed
a
anti-HER2
mAb,
H2Mab-250/H2CasMab-2
(mouse
IgG1,
kappa).
In
this
study,
we
assessed
both
vitro
vivo
efficacy
humanized
H2Mab-250
(humH2Mab-250).
Although
humH2Mab-250
showed
lower
reactivity
HER2-overexpressed
Chinese
hamster
ovary-K1
(CHO/HER2)
breast
cell
lines
(BT-474
SK-BR-3)
than
trastuzumab
flow
cytometry,
similar
antibody-dependent
cellular
cytotoxicity
(ADCC)
against
CHO/HER2
presence
effector
splenocytes.
addition,
exhibited
significant
complement-dependent
(CDC)
compared
trastuzumab.
Furthermore,
possesses
compatible
effects
xenografts
with
These
findings
highlight
distinct
roles
ADCC
CDC
suggest
direction
clinical
development
HER2-positive
tumors.
Язык: Английский
Nanoscale warriors against viral invaders: a comprehensive review of Nanobodies as potential antiviral therapeutics
mAbs,
Год журнала:
2025,
Номер
17(1)
Опубликована: Апрель 9, 2025
Viral
infections
remain
a
significant
global
health
threat,
with
emerging
and
reemerging
viruses
causing
epidemics
pandemics.
Despite
advancements
in
antiviral
therapies,
the
development
of
effective
treatments
is
often
hindered
by
challenges,
such
as
viral
resistance
emergence
new
strains.
In
this
context,
novel
therapeutic
modalities
essential
to
combat
notorious
viruses.
While
traditional
monoclonal
antibodies
are
widely
used
for
treatment
several
diseases,
nanobodies
derived
from
heavy
chain-only
have
emerged
promising
"nanoscale
warriors"
against
infections.
Nanobodies
possess
unique
structural
properties
that
enhance
their
ability
recognize
diverse
epitopes.
Their
small
size
also
imparts
properties,
improved
bioavailability,
solubility,
stability,
proteolytic
resistance,
making
them
an
ideal
class
therapeutics
review,
we
discuss
role
antivirals
various
Techniques
developing
nanobodies,
delivery
strategies
covered,
challenges
opportunities
associated
use
therapies
discussed.
We
offer
insights
into
future
nanobody-based
research
support
managing
Язык: Английский
A Comprehensive Review About the Use of Monoclonal Antibodies in Cancer Therapy
Antibodies,
Год журнала:
2025,
Номер
14(2), С. 35 - 35
Опубликована: Апрель 11, 2025
Monoclonal
antibodies
(mAbs)
targeting
various
pathways
in
cancer
therapy
play
crucial
roles
enhancing
the
immune
system's
ability
to
recognise
and
eliminate
tumour
cells.
These
therapies
are
designed
either
block
inhibitory
checkpoint
or
target
specific
cell
markers
for
direct
destruction.
Additionally,
mAbs
can
modulate
microenvironment,
enhance
antibody-dependent
cellular
cytotoxicity,
inhibit
angiogenesis,
further
amplifying
their
therapeutic
impact.
Below
is
a
summary
of
monoclonal
key
pathways,
along
with
indications
mechanisms
action,
which
reviewed
based
on
mechanisms.
Язык: Английский