The
humanization
of
camelid-derived
variable
domain
heavy
chain
antibodies
(VHHs)
poses
challenges
including
immunogenicity,
stability,
and
potential
reduction
affinity.
Critical
to
this
process
are
complementarity-determining
regions
(CDRs),
Vernier
Hallmark
residues,
shaping
the
three-dimensional
fold
influencing
VHH
structure
function.
Additionally,
presence
non-canonical
disulfide
bonds
further
contributes
conformational
stability
antigen
binding.
In
study,
we
systematically
humanized
two
VHHs
targeting
natural
cytotoxicity
receptor
NKp30.
Key
structural
positions
in
were
exchanged
with
residues
from
most
similar
human
germline
sequences.
resulting
variants
characterized
for
binding
affinities,
yield,
purity.
Structural
modes
elucidated
through
crystal
determination
AlphaFold2
predictions,
providing
insights
into
differences
Comparative
molecular
dynamics
characterizations
selected
performed
rationalize
their
functional
properties
elucidate
role
specific
sequence
motifs
Furthermore,
systematic
analyses
next-generation
sequencing
(NGS)
Protein
Data
Bank
(PDB)
data
was
conducted,
shedding
light
on
significance
general.
Overall,
study
provides
valuable
determinants
governing
VHHs,
offering
a
roadmap
rational
design,
humanization,
optimization
therapeutic
applications.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(6), С. 5994 - 5994
Опубликована: Март 22, 2023
NANOBODY®
(a
registered
trademark
of
Ablynx
N.V)
molecules
(Nbs),
also
referred
to
as
single
domain-based
VHHs,
are
antibody
fragments
derived
from
heavy-chain
only
IgG
antibodies
found
in
the
Journal of Clinical Medicine,
Год журнала:
2023,
Номер
12(4), С. 1630 - 1630
Опубликована: Фев. 17, 2023
Due
to
the
key
role
of
tumor
necrosis
factor-alpha
(TNF-α)
in
pathogenesis
immunoinflammatory
diseases,
TNF-α
inhibitors
have
been
successfully
developed
and
used
clinical
treatment
autoimmune
disorders.
Currently,
five
anti-TNF-α
drugs
approved:
infliximab,
adalimumab,
golimumab,
certolizumab
pegol
etanercept.
Anti-TNF-α
biosimilars
are
also
available
for
use.
Here,
we
will
review
historical
development
as
well
present
potential
future
applications
therapies,
which
led
major
improvements
patients
with
several
such
rheumatoid
arthritis
(RA),
ankylosing
spondylitis
(AS),
Crohn’s
disease
(CD),
ulcerative
colitis
(UC),
psoriasis
(PS)
chronic
endogenous
uveitis.
Other
therapeutic
areas
under
evaluation,
including
viral
infections,
e.g.,
COVID-19,
neuropsychiatric
disorders
certain
forms
cancer.
The
search
biomarkers
able
predict
responsiveness
is
discussed.
Chemical Reviews,
Год журнала:
2023,
Номер
123(12), С. 7782 - 7853
Опубликована: Май 15, 2023
The
high
selectivity
and
affinity
of
antibodies
toward
their
antigens
have
made
them
a
highly
valuable
tool
in
disease
therapy,
diagnosis,
basic
research.
A
plethora
chemical
genetic
approaches
been
devised
to
make
accessible
more
"undruggable"
targets
equipped
with
new
functions
illustrating
or
regulating
biological
processes
precisely.
In
this
Review,
addition
introducing
how
naked
various
antibody
conjugates
(such
as
antibody-drug
conjugates,
antibody-oligonucleotide
antibody-enzyme
etc.)
work
therapeutic
applications,
special
attention
has
paid
chemistry
tools
helped
optimize
the
outcome
(i.e.,
enhanced
efficacy
reduced
side
effects)
facilitate
multifunctionalization
antibodies,
focus
on
emerging
fields
such
targeted
protein
degradation,
real-time
live-cell
imaging,
catalytic
labeling
decaging
spatiotemporal
control
well
engagement
inside
cells.
With
advances
modern
biotechnology,
well-designed
derivatives
via
size
miniaturization
together
efficient
delivery
systems
emerged,
which
gradually
improved
our
understanding
important
paved
way
pursue
novel
for
potential
treatments
diseases.
Journal of Nanobiotechnology,
Год журнала:
2023,
Номер
21(1)
Опубликована: Ноя. 6, 2023
Pancreatic
cancer
is
a
highly
aggressive
malignancy
with
limited
treatment
options
and
poor
prognosis.
Trophoblast
cell
surface
antigen
2
(TROP2),
overexpressed
in
the
tumors
of
more
than
half
pancreatic
patients,
has
been
identified
as
potential
target
for
antibody-drug
conjugates
(ADCs).
Almost
all
reported
TROP2-targeted
ADCs
are
IgG
type
have
poorly
studied
cancer.
Here,
we
aimed
to
develop
novel
nanobody-drug
conjugate
(NDC)
targeting
TROP2
cancer.In
this
study,
developed
NDC,
HuNbTROP2-HSA-MMAE,
TROP2-positive
HuNbTROP2-HSA-MMAE
characterized
by
use
nanobodies
against
human
serum
albumin
(HSA)
drug-antibody
ratio
1.
exhibited
specific
binding
was
internalized
into
tumor
cells
high
endocytosis
efficiency
within
5
h,
followed
intracellular
translocation
lysosomes
release
MMAE
induce
apoptosis
through
caspase-3/9
pathway.
In
xenograft
model
cancer,
doses
0.2
mg/kg
1
demonstrated
significant
antitumor
effects,
dose
even
eradicated
tumor.HuNbTROP2-HSA-MMAE
desirable
affinity,
internalization
activity.
It
holds
promise
therapeutic
option
Bispecific
antibodies
(bsAbs)
are
a
class
of
that
can
mediate
novel
mechanisms
action
compared
to
monospecific
monoclonal
(mAbs).
Since
the
discovery
mAbs
and
their
adoption
as
therapeutic
agents
in
1980s
1990s,
development
bsAbs
has
held
substantial
appeal.
Nevertheless,
only
three
(catumaxomab,
blinatumomab,
emicizumab)
were
approved
through
end
2020.
However,
since
then,
11
received
regulatory
agency
approvals,
which
nine
(amivantamab,
tebentafusp,
mosunetuzumab,
cadonilimab,
teclistamab,
glofitamab,
epcoritamab,
talquetamab,
elranatamab)
for
treatment
cancer
two
(faricimab,
ozoralizumab)
non-oncology
indications.
Notably,
13
currently
bsAbs,
two,
emicizumab
faricimab,
have
achieved
blockbuster
status,
showing
promise
this
therapeutics.
In
2020s,
approval
additional
be
expected
hematological
malignancies,
solid
tumors
indications,
establishing
essential
part
armamentarium.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Окт. 26, 2024
Nanobodies
(Nbs)
are
antibody
fragments
derived
from
heavy-chain-only
IgG
antibodies
found
in
the
Camelidae
family
as
well
cartilaginous
fish.
Their
unique
structural
and
functional
properties,
such
their
small
size,
ability
to
be
engineered
for
high
antigen-binding
affinity,
stability
under
extreme
conditions,
ease
of
production,
have
made
them
promising
tools
diagnostics
therapeutics.
This
potential
was
realized
2018
with
approval
caplacizumab,
world's
first
Nb-based
drug.
Currently,
Nbs
being
investigated
clinical
trials
a
broad
range
treatments,
including
targeted
therapies
against
PDL1
Epidermal
Growth
Factor
Receptor
(EGFR),
cardiovascular
diseases,
inflammatory
neurodegenerative
disorders
Alzheimer's
disease,
Parkinson's
amyotrophic
lateral
sclerosis.
They
also
studied
detecting
imaging
autoimmune
conditions
infectious
diseases
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2).
A
variety
methods
now
available
generate
target-specific
quickly
efficiently
at
low
costs,
increasing
accessibility.
article
examines
these
diverse
applications
roles.
Only
most
recent
articles
published
last
five
years
been
used
summarize
advanced
developments
field.
Among
the
emerging
strategies
for
cancer
theranostics,
nanomedicines
offer
significant
promise
in
advancing
both
patients'
diagnosis
and
treatment.
In
combination
with
nanobodies,
can
potentially
enhance
precision
efficiency
of
drug
or
imaging
agent
delivery,
addressing
key
limitations
current
approaches,
such
as
off-target
toxicities.
The
development
will
be
further
accelerated
by
creation
smart
nanoparticles,
their
integration
immunotherapy.
Obviously,
success
nano-immunotherapy
depend
on
a
comprehensive
understanding
tumor
microenvironment,
including
complex
interplay
mechanisms
that
drive
cancer-mediated
immunosuppression
immune
escape.
Hence,
effective
therapeutic
targeting
microenvironment
requires
modulation
cell
function,
overcoming
resistance
associated
stromal
components
extracellular
matrix,
and/or
direct
elimination
cells.
Identifying
molecules
involved
progression
is,
therefore,
essential
developing
therapies
diagnostic
tools
predict
patient
responses
to
treatment
monitor
outcomes.
Current
are
being
designed
careful
consideration
factors
choice
carrier
(e.g.,
biocompatibility,
controlled
cargo
release)
moiety.
unique
properties
nanobodies
make
them
an
engineering
tool
target
biological
high
affinity
specificity.
this
review,
we
focus
latest
applications
various
purposes.
We
also
explore
main
types
nanoparticles
used
immunotherapies,
well
formulating
nanoparticle-nanobody
conjugates.
Finally,
highlight
how
nanobody-nanoparticle
formulations
nanomedicines.
Expert Opinion on Investigational Drugs,
Год журнала:
2023,
Номер
32(8), С. 705 - 721
Опубликована: Авг. 3, 2023
Introduction
Monoclonal
antibodies
have
revolutionized
personalized
medicine
for
cancer
in
recent
decades.
Despite
their
broad
application
oncology,
large
size
and
complexity
may
interfere
with
successful
tumor
targeting
certain
applications
of
diagnosis
therapy.
Nanobodies
unique
structural
pharmacological
features
compared
to
monoclonal
successfully
been
used
as
complementary
anti-cancer
diagnostic
and/or
therapeutic
tools.Areas
covered
Here,
an
overview
is
given
the
nanobody-based
diagnostics
therapeutics
that
or
are
currently
being
tested
oncological
clinical
trials.
Furthermore,
preclinical
developments,
which
likely
be
translated
into
clinic
near
future,
highlighted.Expert
opinion
Overall,
presented
studies
show
potential
nanobodies
field
making
it
more
will
clinically
approved
upcoming
future.
Immunological Reviews,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 21, 2024
Summary
Heavy‐chain
antibodies
(HCAbs)
are
a
unique
type
of
devoid
light
chains,
and
comprised
two
heavy
chains‐only
that
recognize
their
cognate
antigen
by
virtue
single
variable
domain
also
referred
to
as
VHH,
antibody
(sdAb),
or
nanobody
(Nb).
These
functional
HCAbs,
serendipitous
discovered
about
three
decades
ago,
exclusively
found
in
camelids,
comprising
dromedaries,
camels,
llamas,
vicugnas.
Nanobodies
have
become
an
essential
tool
biomedical
research
medicine,
both
diagnostics
therapeutics
due
beneficial
properties:
small
size,
high
stability,
strong
antigen‐binding
affinity,
low
immunogenicity,
production
cost,
straightforward
engineering
into
more
potent
affinity
reagents.
The
occurrence
HCAbs
camelids
remains
intriguing.
It
is
believed
be
evolutionary
adaptation,
equipping
with
robust
adaptive
immune
defense
suitable
respond
the
pressure
from
pathogenic
invasion
necessitating
profound
recognition
neutralization.
This
innovation
led
simplified
HCAb
structure,
possibly
supported
genetic
mutations
drift,
allowing
mutation
diversification
chain
gene
constant
regions.
Beyond
understanding
origins,
application
nanobodies
has
significantly
advanced
over
past
30
years.
Alongside
expanding
laboratory
research,
there
been
rapid
increase
patent
for
nanobodies.
introduction
commercial
drugs
such
Cablivi,
Nanozora,
Envafolimab,
Carvykti
boosted
confidence
among
potential.
review
explores
history
ontogeny,
applications
biotechnology
pharmaceuticals,
focusing
on
approved
ongoing
medical
pipelines.