Rare Diseases Symptoms Automatic Extraction
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Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse.
[severe combined immunodeficiency]
Rituximab
(
RTX
)
,
a
chimeric
IgG
1
monoclonal
antibody
directed
against
the
CD
2
0
antigen
,
has
revolutionized
the
treatment
of
B-
cell
malignancies
.
Nevertheless
,
the
relapsed
/
refractory
rates
are
still
high
.
One
strategy
to
increase
the
clinical
effectiveness
of
RTX
is
based
on
antibody-cytokine
fusion
protein
(
immunocytokine
;
ICK
)
vectorizing
together
at
the
tumor
site
the
antibody
effector
activities
and
the
cytokine
co
-signal
required
for
the
generation
of
cytotoxic
cellular
immunity
.
Such
ICKs
linking
various
antibody
formats
to
interleukin
(
IL
)
-
2
are
currently
being
investigated
in
clinical
trials
and
have
shown
promising
results
in
cancer
therapies
.
IL
-
15
,
a
structurally-related
cytokine
,
is
now
considered
as
having
a
better
potential
than
IL
-
2
in
antitumor
immunotherapeutic
strategies
.
We
have
previously
engineered
the
fusion
protein
RLI
,
linking
a
soluble
form
of
human
IL
-
15
Rα-sushi
+
domain
to
human
IL
-
15
.
Compared
with
IL
-
15
,
RLI
displayed
better
biological
activities
in
vitro
and
higher
antitumor
effects
in
vivo
in
murine
and
human
cancer
models
.
In
this
study
,
we
investigated
the
advantages
of
fusing
RLI
to
RTX
.
Anti-
CD
2
0
-
RLI
kept
its
binding
capacity
to
CD
2
0
,
CD
16
and
IL
-
15
receptor
and
therefore
fully
retained
both
antibody
effector
functions
(
ADCC
and
CDC
)
,
and
the
cytokine
potential
of
RLI
.
In
a
severe
combined
immunodeficiency
(
SCID
)
mouse
model
of
disseminated
residual
lymphoma
,
anti-
CD
2
0
-
RLI
was
found
to
induce
long
-term
survival
of
90
%
of
mice
up
to
at
least
120
days
whereas
RLI
and
RTX
,
alone
or
in
combination
,
just
delayed
the
disease
onset
(
100
%
of
death
at
28
,
40
and
51
days
respectively
)
.
These
findings
suggest
that
such
ICK
could
improve
the
clinical
efficacy
of
RTX
,
particularly
in
patients
with
refractory
B-
cell
lymphoma
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated