Journal of Biological Chemistry,
Год журнала:
2023,
Номер
300(1), С. 105555 - 105555
Опубликована: Дек. 10, 2023
Discovery
and
optimization
of
a
biotherapeutic
monoclonal
antibody
requires
careful
balance
target
engagement
physicochemical
developability
properties.
To
take
full
advantage
the
sequence
diversity
provided
by
different
discovery
platforms,
rapid
reliable
process
for
humanization
antibodies
from
nonhuman
sources
is
required.
Canonically,
maximizing
homology
human
variable
region
(V-region)
to
original
germline
was
believed
result
in
preservation
binding,
often
without
much
consideration
inherent
molecular
We
expand
on
this
approach
grafting
complementary
determining
regions
(CDRs)
mouse
anti-LAG3
into
an
extensive
matrix
heavy
chain
(VH)
light
(VL)
framework
with
substantially
broader
assess
impact
region-framework
compatibility
through
progressive
evaluation
expression,
affinity,
biophysical
developability,
function.
Specific
VH
VL
sequences
were
associated
major
expression
purification
phenotypes.
Greater
conservation
correlated
retained
or
improved
affinity.
Analysis
grafts
that
bound
demonstrated
initial
criteria
significantly
impacted
VH,
but
not
VL.
In
contrast,
cell
binding
functional
characteristics
VL,
VH.
Principal
component
analysis
all
factors
identified
multiple
exhibited
more
favorable
properties,
notably
nonoptimal
conservation.
Overall,
study
demonstrates
modern
throughput
systems
enable
thorough,
customizable,
systematic
graft-framework
combinations,
resulting
humanized
global
properties
may
progress
development
quickly
greater
probability
success.
Abstract
Breast
cancer,
the
most
frequent
female
malignancy,
is
often
curable
when
detected
at
an
early
stage.
The
treatment
of
metastatic
breast
cancer
more
challenging
and
may
be
unresponsive
to
conventional
therapy.
Immunotherapy
crucial
for
treating
but
its
resistance
a
major
limitation.
tumor
microenvironment
(TME)
vital
in
modulating
immunotherapy
response.
Various
microenvironmental
components,
such
as
cancer-associated
fibroblasts
(CAFs),
tumor-associated
macrophages
(TAMs),
myeloid-derived
suppressor
cells
(MDSCs),
are
involved
TME
modulation
cause
resistance.
This
review
highlights
role
stromal
microenvironment,
including
involvement
CAF-TAM
interaction,
alteration
metabolism
leading
failure,
other
latest
strategies,
high
throughput
genomic
screening,
single-cell
spatial
omics
techniques
identifying
immune
genes
regulating
emphasizes
therapeutic
approach
overcome
through
CAF
reprogramming,
TAM
polarization,
metabolism,
alterations.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 4, 2024
Immunotherapy
has
been
developed,
which
harnesses
and
enhances
the
innate
powers
of
immune
system
to
fight
disease,
particularly
cancer.
PD-1
(programmed
death-1)
PD-L1
death
ligand-1)
are
key
components
in
regulation
system,
context
cancer
immunotherapy.
regulated
by
PTMs,
including
phosphorylation,
ubiquitination,
deubiquitination,
acetylation,
palmitoylation
glycosylation.
PROTACs
(Proteolysis
Targeting
Chimeras)
a
type
new
drug
design
technology.
They
specifically
engineered
molecules
that
target
specific
proteins
within
cell
for
degradation.
have
designed
demonstrated
their
inhibitory
activity
against
PD-1/PD-L1
pathway,
showed
ability
degrade
proteins.
In
this
review,
we
describe
how
improve
efficacy
could
be
novel
strategy
combine
with
radiotherapy,
chemotherapy
immunotherapy
patients.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 24, 2025
Predicting
disease
prognosis
and
the
efficacy
of
immunotherapy
presents
a
significant
challenge
in
treatment
hepatocellular
carcinoma
(HCC).
By
analyzing
transcriptome
sequencing
data
from
69
patients
identifying
differentially
expressed
immune
genes,
prognostic
index
named
immune-related
gene
(IRGPI)
was
established
by
Lasso-Cox
regression.
The
IRGPI,
which
consists
six
key
found
to
be
predictor
poor
with
high
IRGPI
scores.
model's
predictive
accuracy
confirmed
via
receiver
operating
characteristic
(ROC)
curve
analysis,
area
under
(AUC)
values
0.85,
0.779,
0.857
for
1-,
3-,
5-year
survival
predictions,
respectively.
Additionally,
scores
had
increased
levels
Treg
cells
neutrophils,
advanced
tumor
staging,
microvascular
invasion
grading,
checkpoint
expression.
also
effective
predicting
IMvigor210
dataset,
demonstrating
its
potential
as
valuable
tool
assessing
patient
guiding
strategies
HCC.
Cancers,
Год журнала:
2025,
Номер
17(8), С. 1260 - 1260
Опубликована: Апрель 8, 2025
Human
papillomavirus
(HPV)-related
lower
genital
cancers,
including
cervical
cancer,
anal
squamous
cell
carcinoma
(SCC),
vaginal
vulvar
and
penile
pose
a
significant
health
burden,
with
approximately
45,000
new
cases
diagnosed
annually.
Current
effective
treatment
modalities
include
chemoradiotherapy,
systemic
chemotherapy,
immune
checkpoint
inhibitors
(ICIs).
The
tumor
microenvironment
in
HPV-related
cancers
is
characterized
by
evasion
mechanisms,
the
modulation
of
checkpoints
such
as
PD-L1/PD-1.
HPV
oncoproteins
E5,
E6,
E7
play
crucial
roles
this
process,
altering
expression
inhibitory
molecules
recruitment
cells.
ICIs,
programmed
death
protein
1
(PD-1)
inhibitors,
have
shown
efficacy
enhancing
response
against
HPV-associated
tumors
blocking
proteins
that
allow
cancer
cells
to
evade
surveillance.
Recent
studies
demonstrated
HPV-positive
exhibit
more
favorable
ICI-based
therapies
compared
HPV-negative
tumors.
integration
ICIs
into
regimens
for
has
been
supported
several
clinical
trials.
inclusion
approach
presents
promising
opportunity
improving
patient
outcomes.
Ongoing
research
trials
are
advancing
our
understanding
therapeutic
potential
immunotherapy
these
cancers.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 29, 2024
Brain
metastatic
cancer
poses
a
significant
clinical
challenge,
with
limited
treatment
options
and
poor
prognosis
for
patients.
In
recent
years,
immunotherapy
has
emerged
as
promising
strategy
addressing
brain
metastases,
offering
distinct
advantages
over
conventional
treatments.
This
review
explores
the
evolving
landscape
of
tumor
in
context
cancer,
focusing
on
intricate
interplay
between
microenvironment
(TME)
immunotherapeutic
approaches.
By
elucidating
complex
interactions
within
TME,
including
role
immune
cells,
cytokines,
extracellular
matrix
components,
this
highlights
potential
to
reshape
paradigm
metastases.
Leveraging
checkpoint
inhibitors,
cellular
immunotherapies,
personalized
strategies,
holds
promise
overcoming
challenges
posed
by
blood-brain
barrier
immunosuppressive
Through
comprehensive
analysis
current
research
findings
future
directions,
underscores
transformative
impact
management
new
insights
opportunities
precise
therapeutic
interventions.
Bioengineering,
Год журнала:
2024,
Номер
12(1), С. 7 - 7
Опубликована: Дек. 25, 2024
In
spite
of
significant
advancements
in
diagnosis
and
treatment,
cancer
remains
one
the
major
threats
to
human
health
due
its
ability
cause
disease
with
high
morbidity
mortality.
A
multifactorial
multitargeted
approach
is
required
towards
intervention
multitude
signaling
pathways
associated
carcinogenesis
inclusive
angiogenesis
metastasis.
this
context,
plants
provide
an
immense
source
phytotherapeutics
that
show
great
promise
as
anticancer
drugs.
There
increasing
epidemiological
data
indicating
diets
rich
vegetables
fruits
could
decrease
risks
certain
cancers.
Several
studies
have
proved
natural
plant
polyphenols,
such
flavonoids,
lignans,
phenolic
acids,
alkaloids,
phenylpropanoids,
isoprenoids,
terpenes,
stilbenes,
be
used
prophylaxis
therapeutics
by
recruitment
mechanisms
antioxidant
anti-inflammatory
activities
modulation
several
molecular
events
carcinogenesis.
The
current
review
discusses
principal
phytochemicals
focus
on
circuits
targeted
therapy.
Also
addressed
are
plant-derived
anti-cancer
vaccines,
nanoparticles,
monoclonal
antibodies,
immunotherapies.
This
article
brings
light
importance
plant-based
platforms
invaluable,
low-cost
sources
molecules
particular
applicability
resource-poor
developing
countries.
