Journal for ImmunoTherapy of Cancer,
Journal Year:
2025,
Volume and Issue:
13(1), P. e010059 - e010059
Published: Jan. 1, 2025
Nivolumab
is
an
immune
checkpoint
inhibitor
(ICI)
that
selectively
inhibits
programmed
cell
death
protein
1
activation,
restoring
antitumor
immunity.
ICIs
are
indicated
for
various
types
of
advanced
solid
tumors;
however,
not
all
patients
benefit
from
them,
and
tools
could
be
used
in
the
clinic
to
predict
response
treatment
represent
unmet
need.
Here
we
describe
development
a
new
population
pharmacokinetic
(PPK)
model
treated
with
nivolumab
clinical
trials.
Applying
patient
renal
carcinoma
identified
clearance
plasma
concentration
as
predictors
overall
survival
(OS).
A
custom
liquid
chromatography
tandem
mass
spectrometry
method
quantifying
was
developed
validated
following
European
Medicines
Agency
guidelines
bioanalytical
validation.
The
PPK
using
data
NIVIPIT
(n=38)
NIVOREN
(n=137)
trials
metastatic
melanoma
carcinoma,
respectively.
determine
(PK)
parameters
such
baseline
simulate
individual
changes
over
time.
relationship
between
PK
characteristics
(including
at
Cycle
(CLC1),
3
outcomes
assessed
137
NIVOREN.
Kaplan-Meier
methodology
time-to-event
analyses.
In
patients,
median
CLC1
6
mL/hour
48
µg/mL.
Median
follow-up
21.0
months
(95%
CI
20.2
22.5
months)
rate
91.2%
77.9%
12
months.
univariate
analysis,
OS
significantly
higher
CLC1<6
versus
≥6
(HR
2.2
1.2
4.1),
p=0.0146).
Shorter
observed
below
(48
µg/mL)
those
above
0.4
0.2
0.8),
p=0.0069).
Multivariate
analysis
showed
trend
towards
lower
clearance,
but
this
did
reach
statistical
significance
(p=0.0694).
Results
study
may
potentially
therapy
carcinoma.
Additional
applications
include
guiding
dose
adjustments
who
less
likely
respond
initial
dose.
JAMA,
Journal Year:
2023,
Volume and Issue:
330(21), P. 2064 - 2064
Published: Dec. 5, 2023
Importance
Gastric
and
gastroesophageal
junction
cancers
are
diagnosed
in
more
than
1
million
people
worldwide
annually,
few
effective
treatments
available.
Sintilimab,
a
recombinant
human
IgG4
monoclonal
antibody
that
binds
to
programmed
cell
death
(PD-1),
combination
with
chemotherapy,
has
demonstrated
promising
efficacy.
Objective
To
compare
overall
survival
of
patients
unresectable
locally
advanced
or
metastatic
gastric
who
were
treated
sintilimab
chemotherapy
vs
placebo
chemotherapy.
Also
compared
subset
PD
ligand
(PD-L1)
combined
positive
score
(CPS)
5
(range,
1-100).
Design,
Setting,
Participants
Randomized,
double-blind,
placebo-controlled,
phase
3
clinical
trial
conducted
at
62
hospitals
China
enrolled
650
adenocarcinoma
between
January
3,
2019,
August
5,
2020.
Final
follow-up
occurred
on
June
20,
2021.
Interventions
Patients
randomized
1:1
either
(n
=
327)
323)
capecitabine
oxaliplatin
(the
XELOX
regimen)
every
weeks
for
maximum
6
cycles.
Maintenance
therapy
plus
continued
up
2
years.
Main
Outcomes
Measures
The
primary
end
point
was
time
from
randomization.
Results
Of
the
(mean
age,
59
years;
483
[74.3%]
men),
327
323
Among
patients,
397
(61.1%)
had
tumors
PD-L1
CPS
more;
563
(86.6%)
discontinued
study
treatment
388
(59.7%)
died;
patient
(&lt;0.1%)
lost
follow-up.
all
improved
(median,
15.2
12.3
months;
stratified
hazard
ratio
[HR],
0.77
[95%
CI,
0.63-0.94];
P
.009).
more,
18.4
12.9
HR,
0.66
0.50-0.86];
.002).
most
common
grade
higher
treatment-related
adverse
events
decreased
platelet
count
(sintilimab,
24.7%
placebo,
21.3%),
neutrophil
20.1%
18.8%),
anemia
12.5%
8.8%).
Conclusions
Relevance
first-line
significantly
placebo.
Trial
Registration
ClinicalTrials.gov
Identifier:
NCT03745170
Frontiers in Pharmacology,
Journal Year:
2023,
Volume and Issue:
14
Published: Sept. 18, 2023
Antibody-Drug
Conjugates
(ADCs)
represent
an
innovative
class
of
potent
anti-cancer
compounds
that
are
widely
used
in
the
treatment
hematologic
malignancies
and
solid
tumors.
Unlike
conventional
chemotherapeutic
drug-based
therapies,
mainly
associated
with
modest
specificity
therapeutic
benefit,
three
key
components
form
ADC
(a
monoclonal
antibody
bound
to
a
cytotoxic
drug
via
chemical
linker
moiety)
achieve
remarkable
improvement
terms
targeted
killing
cancer
cells
and,
while
sparing
healthy
tissues,
reduction
systemic
side
effects
caused
by
off-tumor
toxicity.
Based
on
their
beneficial
mechanism
action,
15
ADCs
have
been
approved
date
market
approval
Food
Drug
Administration
(FDA),
European
Medicines
Agency
(EMA)
and/or
other
international
governmental
agencies
for
use
clinical
oncology,
hundreds
undergoing
evaluation
preclinical
phases.
Here,
our
aim
is
provide
comprehensive
overview
features
revolving
around
strategy
including
structural
targeting
properties,
role
tumor
microenvironment
review
providing
discussion
regarding
toxicity
profile,
manifestations
novel
combination
therapies.
Finally,
we
briefly
pathological
contexts
information
manufacturing
analytical
characterization.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Dec. 1, 2023
PD-1
(Programmed
Cell
Death
Protein-1)
and
PD-L1
Ligand-1)
play
a
crucial
role
in
regulating
the
immune
system
preventing
autoimmunity.
Cancer
cells
can
manipulate
this
system,
allowing
them
to
escape
detection
promote
tumor
growth.
Therapies
targeting
PD-1/PD-L1
pathway
have
transformed
cancer
treatment
demonstrated
significant
effectiveness
against
various
types.
This
study
delves
into
structure
signaling
dynamics
of
its
ligands
PD-L1/PD-L2,
diverse
inhibitors
their
efficacy,
resistance
observed
some
patients.
Furthermore,
explored
challenges
associated
with
inhibitor
approach.
Recent
advancements
combination
immunotherapy
chemotherapy,
radiation,
surgical
procedures
enhance
patient
outcomes
also
been
highlighted.
Overall,
offers
an
in-depth
overview
significance
future
implications
oncology.
Journal of Translational Medicine,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: Oct. 2, 2023
Cancer
stem
cells
(CSCs)
have
emerged
as
key
contributors
to
tumor
initiation,
growth,
and
metastasis.
In
addition,
CSCs
play
a
significant
role
in
inducing
immune
evasion,
thereby
compromising
the
effectiveness
of
cancer
treatments.
The
reciprocal
communication
between
microenvironment
(TME)
is
observed,
with
TME
providing
supportive
niche
for
CSC
survival
self-renewal,
while
CSCs,
turn,
influence
polarization
persistence
TME,
promoting
an
immunosuppressive
state.
Consequently,
these
interactions
hinder
efficacy
current
therapies,
necessitating
exploration
novel
therapeutic
approaches
modulate
target
CSCs.
this
review,
we
highlight
intricate
strategies
employed
by
evade
surveillance
develop
resistance
therapies.
Furthermore,
examine
dynamic
interplay
shedding
light
on
how
interaction
impacts
progression.
Moreover,
provide
overview
advanced
that
specifically
which
hold
promise
future
clinical
translational
studies
treatment.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(21), P. 3689 - 3689
Published: Oct. 31, 2024
The
identification
of
reliable
prognostic
biomarkers
is
crucial
for
optimizing
cancer
treatment
strategies,
especially
in
the
era
personalized
medicine.
This
systematic
review
and
meta-analysis
evaluate
significance
neutrophil-to-eosinophil
ratio
(NER)
various
types,
with
a
focus
on
its
association
overall
survival
(OS)
progression-free
(PFS).
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: May 16, 2023
Programmed
cell
death
1
receptor
(PD-1)
and
its
ligands
constitute
an
inhibitory
pathway
to
mediate
the
mechanism
of
immune
tolerance
provide
homeostasis.
Significantly,
binding
partners
PD-1
associated
are
diverse,
which
facilitates
immunosuppression
in
cooperation
with
other
checkpoint
proteins.
Accumulating
evidence
has
demonstrated
important
immunosuppressive
role
axis
tumor
microenvironment
autoimmune
diseases.
In
addition,
blockades
have
been
approved
treat
various
cancers,
including
solid
tumors
hematological
malignancies.
Here,
we
a
comprehensive
review
pathway,
focusing
on
structure
expression
PD-1,
programmed
ligand
(PD-L1),
2
(PD-L2);
diverse
biological
functions
signaling
health
immune-related
diseases
(including
immunity,
autoimmunity,
infectious
transplantation
allergy
privilege);
adverse
events
related
PD-L1
inhibitors.
Cellular and Molecular Immunology,
Journal Year:
2024,
Volume and Issue:
21(10), P. 1089 - 1108
Published: Aug. 12, 2024
Abstract
In
the
past
decade,
chimeric
antigen
receptor
(CAR)-T
cell
therapy
has
emerged
as
a
promising
immunotherapeutic
approach
for
combating
cancers,
demonstrating
remarkable
efficacy
in
relapsed/refractory
hematological
malignancies
both
pediatric
and
adult
patients.
CAR-natural
killer
(CAR-NK)
complements
CAR-T
by
offering
several
distinct
advantages.
CAR-NK
cells
do
not
require
HLA
compatibility
exhibit
low
safety
concerns.
Moreover,
are
conducive
to
“off-the-shelf”
therapeutics,
providing
significant
logistic
advantages
over
cells.
Both
have
shown
consistent
results
malignancies.
However,
their
against
solid
tumors
remains
limited
due
various
obstacles
including
tumor
trafficking
infiltration,
well
an
immuno-suppressive
microenvironment.
this
review,
we
discuss
recent
advances
current
challenges
of
immunotherapies,
with
specific
focus
on
application
tumors.
We
also
analyze
depth
drawbacks
compared
highlight
CAR
optimization.
Finally,
explore
future
perspectives
these
adoptive
highlighting
increasing
contribution
cutting-edge
biotechnological
tools
shaping
next
generation
cellular
immunotherapy.
Advanced Materials,
Journal Year:
2024,
Volume and Issue:
36(21)
Published: Feb. 16, 2024
Immunotherapy
represents
a
revolutionary
paradigm
in
cancer
management,
showcasing
its
potential
to
impede
tumor
metastasis
and
recurrence.
Nonetheless,
challenges
including
limited
therapeutic
efficacy
severe
immune-related
side
effects
are
frequently
encountered,
especially
solid
tumors.
Hydrogels,
class
of
versatile
materials
featuring
well-hydrated
structures
widely
used
biomedicine,
offer
promising
platform
for
encapsulating
releasing
small
molecule
drugs,
biomacromolecules,
cells
controlled
manner.
Immunomodulatory
hydrogels
present
unique
capability
augmenting
immune
activation
mitigating
systemic
toxicity
through
encapsulation
multiple
components
localized
administration.
Notably,
based
on
biopolymers
have
gained
significant
interest
owing
their
biocompatibility,
environmental
friendliness,
ease
production.
This
review
delves
into
the
recent
advances
bio-based
immunotherapy
synergistic
combinatorial
approaches,
highlighting
diverse
applications.
It
is
anticipated
that
this
will
guide
rational
design
field
immunotherapy,
fostering
clinical
translation
ultimately
benefiting
patients.
Frontiers in Science,
Journal Year:
2024,
Volume and Issue:
2
Published: April 4, 2024
Global
warming
and
climate
change
have
increased
the
pollen
burden
frequency
intensity
of
wildfires,
sand
dust
storms,
thunderstorms,
heatwaves—with
concomitant
increases
in
air
pollution,
heat
stress,
flooding.
These
environmental
stressors
alter
human
exposome
trigger
complex
immune
responses.
In
parallel,
pollutants,
allergens,
other
factors
increase
risks
skin
mucosal
barrier
disruption
microbial
dysbiosis,
while
a
loss
biodiversity
reduced
exposure
to
diversity
impairs
tolerogenic
development.
The
resulting
dysregulation
is
contributing
an
immune-mediated
diseases
such
as
asthma
allergic
diseases,
autoimmune
cancer.
It
now
abundantly
clear
that
multisectoral,
multidisciplinary,
transborder
efforts
based
on
Planetary
Health
One
approaches
(which
consider
dependence
health
environment
natural
ecosystems)
are
urgently
needed
adapt
mitigate
effects
change.
Key
actions
include
reducing
emissions
improving
quality
(through
fossil
fuel
use),
providing
safe
housing
(e.g.,
weatherization),
diets
(i.e.,
diversity)
agricultural
practices,
increasing
green
spaces.
There
also
pressing
need
for
collaborative,
multidisciplinary
research
better
understand
pathophysiology
context
New
data
science
techniques,
biomarkers,
economic
models
should
be
used
measure
impact
disease,
inform
mitigation
adaptation
efforts,
evaluate
their
effectiveness.
Justice,
equity,
diversity,
inclusion
(JEDI)
considerations
integral
these
address
disparities
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(14), P. 7517 - 7517
Published: July 9, 2024
Breast
cancer
is
a
disease
encompassing
spectrum
of
molecular
subtypes
and
clinical
presentations,
each
with
distinct
prognostic
implications
treatment
responses.
has
traditionally
been
considered
an
immunologically
"cold"
tumor,
unresponsive
to
immunotherapy.
However,
trials
in
recent
years
have
found
immunotherapy
be
efficacious
therapeutic
option
for
select
patients.
categorized
into
different
ranging
from
the
most
common
positive
hormone
receptor
(HR+),
human
epidermal
growth
factor
2
(HER2)-negative
type,
less
frequent
HER2-
breast
triple-negative
(TNBC),
highlighting
necessity
tailored
strategies
aimed
at
maximizing
patient
outcomes.
Despite
notable
progress
early
detection
new
modalities,
remains
second
leading
cause
death
USA.
Moreover,
decades,
incidence
rates
increasing,
especially
women
younger
than
age
50.
This
prompted
exploration
approaches
address
this
trend,
offering
prospects
Immunotherapy
class
agents
that
revolutionized
landscape
many
cancers,
namely
melanoma,
lung
cancer,
gastroesophageal
amongst
others.
Though
belatedly,
entered
armamentarium
approval
pembrolizumab
combination
chemotherapy
(TNBC)
neoadjuvant
advanced
settings,
thereby
paving
path
further
research
integration
immune
checkpoint
inhibitors
other
cancer.
Trials
exploring
various
therapies
harness
power
symbiosis
chemotherapeutic
are
ongoing
hopes
improving
response
prolonging
survival
Biomarkers
precise
selection
utilization
remain
cardinal
currently
under
investigation,
some
biomarkers
showing
promise,
such
as
Program
Death
Lignat-1
(PDL-1)
Combined
Positive
Score,
Tumor
Mutation
Burden
(TMB),
Infiltrating
Lymphocytes
(TILs).
review
will
present
current
immunotherapy,
particularly
inhibitors,
types