Nature Cancer,
Journal Year:
2022,
Volume and Issue:
4(2), P. 203 - 221
Published: Dec. 30, 2022
We
conducted
integrative
somatic-germline
analyses
by
deeply
sequencing
864
cancer-associated
genes,
complete
genomes
and
transcriptomes
for
300
mostly
previously
treated
children
adolescents/young
adults
with
cancer
of
poor
prognosis
or
rare
tumors
enrolled
in
the
SickKids
Cancer
Sequencing
(KiCS)
program.
Clinically
actionable
variants
were
identified
56%
patients.
Improved
diagnostic
accuracy
led
to
modified
management
a
subset.
Therapeutically
targetable
(54%
patients)
unanticipated
timing
type,
over
20%
derived
from
germline.
Corroborating
mutational
signatures
(SBS3/BRCAness)
patients
germline
homologous
recombination
defects
demonstrates
potential
utility
PARP
inhibitors.
Mutational
burden
was
significantly
elevated
9%
Sequential
sampling
changes
therapeutically
drivers
one-third
patients,
suggesting
benefit
rebiopsy
genomic
analysis
at
time
relapse.
Comprehensive
profiling
is
useful
multiple
points
care
trajectory
cancer,
supporting
its
integration
into
early
clinical
management.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2019,
Volume and Issue:
38(1)
Published: June 19, 2019
Immunotherapy
has
become
an
established
pillar
of
cancer
treatment
improving
the
prognosis
many
patients
with
a
broad
variety
hematological
and
solid
malignancies.
The
two
main
drivers
behind
this
success
are
checkpoint
inhibitors
(CPIs)
chimeric
antigen
receptor
(CAR)
T
cells.
This
review
summarizes
seminal
findings
from
clinical
translational
studies
recently
presented
or
published
at
important
meetings
in
top-tier
journals,
respectively.
For
blockade,
current
focus
on
combinational
approaches,
perioperative
use,
new
tumor
entities,
response
prediction,
toxicity
management
use
special
patient
populations.
Regarding
cellular
immunotherapy,
recent
confirmed
safety
efficacy
CAR
cells
larger
cohorts
acute
lymphoblastic
leukemia
diffuse
large
B
cell
lymphoma.
Different
strategies
to
translate
striking
malignancies
other
types
currently
under
investigation.
regional
distribution
registered
immunotherapy
trials
shift
PD-1
/
PD-L1
(mainly
performed
US
Europe)
(majority
China)
can
be
noted.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Jan. 6, 2023
Abstract
Recent
advances
in
neoantigen
research
have
accelerated
the
development
and
regulatory
approval
of
tumor
immunotherapies,
including
cancer
vaccines,
adoptive
cell
therapy
antibody-based
therapies,
especially
for
solid
tumors.
Neoantigens
are
newly
formed
antigens
generated
by
cells
as
a
result
various
tumor-specific
alterations,
such
genomic
mutation,
dysregulated
RNA
splicing,
disordered
post-translational
modification,
integrated
viral
open
reading
frames.
recognized
non-self
trigger
an
immune
response
that
is
not
subject
to
central
peripheral
tolerance.
The
quick
identification
prediction
neoantigens
been
made
possible
advanced
next-generation
sequencing
bioinformatic
technologies.
Compared
tumor-associated
antigens,
highly
immunogenic
provide
emerging
targets
personalized
serve
prospective
predictors
survival
prognosis
checkpoint
blockade
responses.
therapies
will
be
aided
understanding
mechanism
underlying
neoantigen-induced
anti-tumor
streamlining
process
neoantigen-based
immunotherapies.
This
review
provides
overview
on
characterization
outlines
clinical
applications
immunotherapeutic
strategies
based
neoantigens.
We
also
explore
their
current
status,
inherent
challenges,
translation
potential.
Journal of Hematology & Oncology,
Journal Year:
2019,
Volume and Issue:
12(1)
Published: Sept. 6, 2019
Tumor
neoantigen
is
the
truly
foreign
protein
and
entirely
absent
from
normal
human
organs/tissues.
It
could
be
specifically
recognized
by
neoantigen-specific
T
cell
receptors
(TCRs)
in
context
of
major
histocompatibility
complexes
(MHCs)
molecules.
Emerging
evidence
has
suggested
that
neoantigens
play
a
critical
role
tumor-specific
cell-mediated
antitumor
immune
response
successful
cancer
immunotherapies.
From
theoretical
perspective,
an
ideal
immunotherapy
target
because
they
are
distinguished
germline
as
non-self
host
system.
Neoantigen-based
therapeutic
personalized
vaccines
adoptive
transfer
have
shown
promising
preliminary
results.
Furthermore,
recent
studies
significant
escape,
immunoediting,
sensitivity
to
checkpoint
inhibitors.
In
this
review,
we
systematically
summarize
advances
understanding
identification
its
on
current
We
also
discuss
ongoing
development
strategies
based
future
clinical
applications.
