medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2021,
Номер
unknown
Опубликована: Сен. 13, 2021
Abstract
Late-stage
cancer
immunotherapy
trials
often
lead
to
unusual
survival
curve
shapes,
like
delayed
separation
or
a
plateauing
in
the
treatment
arm.
It
is
critical
for
trial
success
anticipate
such
effects
advance
and
adjust
design
accordingly.
Here,
we
use
silico
–
simulated
based
on
three
different
mathematical
models
assemble
virtual
patient
cohorts
undergoing
late-stage
immunotherapy,
chemotherapy,
combination
therapies.
We
find
that
all
simulation
predict
distinctive
shapes
commonly
associated
with
immunotherapies.
Considering
four
aspects
of
clinical
sample
size,
endpoint,
randomization
rate,
interim
analyses
demonstrate
how,
by
simulating
various
possible
scenarios,
robustness
choices
can
be
scrutinized,
pitfalls
identified
advance.
provide
readily
usable,
web-based
implementations
our
facilitate
their
biomedical
researchers,
doctors,
trialists.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Апрель 24, 2023
Abstract
Late-stage
cancer
immunotherapy
trials
often
lead
to
unusual
survival
curve
shapes,
like
delayed
separation
or
a
plateauing
in
the
treatment
arm.
It
is
critical
for
trial
success
anticipate
such
effects
advance
and
adjust
design
accordingly.
Here,
we
use
silico
–
simulated
based
on
three
different
mathematical
models
assemble
virtual
patient
cohorts
undergoing
late-stage
immunotherapy,
chemotherapy,
combination
therapies.
We
find
that
all
simulation
predict
distinctive
shapes
commonly
associated
with
immunotherapies.
Considering
four
aspects
of
clinical
sample
size,
endpoint,
randomization
rate,
interim
analyses
demonstrate
how,
by
simulating
various
possible
scenarios,
robustness
choices
can
be
scrutinized,
pitfalls
identified
advance.
provide
readily
usable,
web-based
implementations
our
facilitate
their
biomedical
researchers,
doctors,
trialists.
Blood Advances,
Год журнала:
2023,
Номер
7(16), С. 4608 - 4618
Опубликована: Май 1, 2023
We
examined
the
meaning
of
metabolically
active
lesions
on
1-month
restaging
nuclear
imaging
patients
with
relapsed/refractory
large
B-cell
lymphoma
receiving
axicabtagene
ciloleucel
(axi-cel)
by
assessing
relationship
between
total
metabolic
tumor
volume
(MTV)
positron
emission
tomography
(PET)
scans
and
circulating
DNA
(ctDNA)
in
plasma.
In
this
prospective
multicenter
sample
collection
study,
MTV
was
retrospectively
calculated
via
commercial
software
at
baseline,
1,
3
months
after
chimeric
antigen
receptor
(CAR)
T-cell
therapy;
ctDNA
available
before
axi-cel
administration.
Spearman
correlation
coefficient
(rs)
used
to
study
variables,
a
mathematical
model
constructed
describe
dynamics
1
month
CAR
therapy.
The
median
time
baseline
scan
infusion
33
days
(range,
1-137
days)
for
all
57
patients.
For
41
within
or
that
but
no
bridging
therapy,
became
stronger
(rs,
0.61;
P
<
.0001)
compared
0.38;
=
.004).
Excluding
complete
remission
measurable
residual
disease,
did
not
correlate
0.28;
.11)
correlated
0.79;
.0007).
Modeling
dynamics,
which
incorporated
inflammation
as
part
MTV,
recapitulated
outcomes
positive
radiologic
scans.
Our
results
suggested
nonprogressing
hypermetabolic
PET
represent
ongoing
treatment
responses,
their
composition
may
be
elucidated
concurrently
examining
ctDNA.
Immunology,
Год журнала:
2023,
Номер
170(4), С. 453 - 469
Опубликована: Июль 12, 2023
Abstract
Hepatocellular
carcinoma
(HCC)
remains
a
global
health
challenge.
Novel
treatment
modalities
are
urgently
needed
to
extend
the
overall
survival
of
patients.
The
liver
plays
an
immunomodulatory
function
due
its
unique
physiological
structural
characteristics.
Therefore,
following
surgical
resection
and
radiotherapy,
immunotherapy
regimens
have
shown
great
potential
in
hepatocellular
carcinoma.
Adoptive
cell
is
rapidly
developing
In
this
review,
we
summarize
latest
research
on
adoptive
for
focus
chimeric
antigen
receptor
(CAR)‐T
cells
T
(TCR)
engineered
cells.
Then
tumour‐infiltrating
lymphocytes
(TILs),
natural
killer
(NK)
cells,
cytokine‐induced
(CIK)
macrophages
briefly
discussed.
main
overview
application
challenges
It
aims
provide
reader
with
comprehensive
understanding
current
status
HCC
offers
some
strategies.
We
hope
new
ideas
clinical
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Май 10, 2024
Currently,
therapies
such
as
chimeric
antigen
receptor-T
Cell
(CAR-T)
and
immune
checkpoint
inhibitors
like
programmed
cell
death
protein-1
(PD-1)
blockers
are
showing
promising
results
for
numerous
cancer
patients.
However,
significant
advancements
required
before
CAR-T
become
readily
available
off-the-shelf
treatments,
particularly
solid
tumors
lymphomas.
In
this
review,
we
have
systematically
analyzed
the
combination
therapy
involving
engineered
cells
anti
PD-1
agents.
This
approach
aims
at
overcoming
limitations
of
current
treatments
offers
potential
advantages
enhanced
tumor
inhibition,
alleviated
T-cell
exhaustion,
heightened
activation,
minimized
toxicity.
The
integration
therapy,
which
targets
tumor-associated
antigens,
with
blockade
augments
function
mitigates
suppression
within
microenvironment.
To
assess
impact
on
various
lymphomas,
categorized
them
based
six
major
antigens:
mesothelin,
disialoganglioside
GD-2,
CD-19,
CD-22,
CD-133,
CD-30,
present
in
different
types.
We
evaluated
efficacy,
complete
partial
responses,
progression-free
survival
both
pre-clinical
clinical
models.
Additionally,
discussed
implications,
including
feasibility
immunotherapies,
emphasizing
importance
ongoing
research
to
optimize
treatment
strategies
improve
outcomes
Overall,
believe
combining
holds
promise
next
generation
immunotherapy.
Frontiers in Immunology,
Год журнала:
2024,
Номер
14
Опубликована: Янв. 19, 2024
The
release
of
tumor
antigens
during
traditional
cancer
treatments
such
as
radio-
or
chemotherapy
leads
to
a
stimulation
the
immune
response
which
provides
synergistic
effects
these
have
when
combined
with
immunotherapies.
A
low-dimensional
mathematical
model
is
formulated
which,
depending
on
values
its
parameters,
encompasses
3
E’s
(elimination,
equilibrium,
escape)
system
interactions.
For
escape
situation,
optimal
control
problems
are
aim
revert
process
equilibrium
scenario.
Some
numerical
results
included.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 12, 2024
ABSTRACT
Direct
observation
of
immune
cell
trafficking
patterns
and
tumor-immune
interactions
is
unlikely
in
human
tumors
with
currently
available
technology,
but
computational
simulations
based
on
clinical
data
can
provide
insight
to
test
hypotheses.
It
hypothesized
that
collagen
formation
evolve
as
a
mechanism
escape,
the
exact
nature
interaction
between
cells
poorly
understood.
Spatial
quantifying
degree
fiber
alignment
squamous
carcinomas
indicates
late
stage
disease
associated
highly
aligned
fibers.
Here,
we
introduce
modeling
framework
(called
Lenia)
discriminate
two
hypotheses:
migration
moves
1)
parallel
or
2)
perpendicular
orientation.
The
recapitulates
immune-ECM
where
protection,
leading
an
emergent
inverse
relationship
coverage.
We
also
illustrate
capabilities
Lenia
model
evolution
tumor
progression
predation.
provides
flexible
for
considering
spectrum
local
(cell-scale)
global
(tumor-scale)
dynamics
by
defining
kernel
cell-cell
function
governs
growth
under
predation
migration.
Mathematical
important
mechanistic
insights
into
interactions.
Short-range
kernels
survival
conditions
strong
Allee
effects,
while
asymmetric
lead
poor
response.
Thus,
length
scale
drives
infiltration.
