Medical Design Briefs - January 2024 - 31

Moving the Needle on Monitoring Skin Cancer
Microneedles allow for
the monitoring of protein
biomarkers.
Harvard University Wyss
Institute
Boston, MA
Patients with melanoma, the most
concerning form of skin cancer in which
pigment- producing cells start to grow
out of control, can benefit from existing
immuno therapies, but by far not all of
them do. More than 50 percent of patients
do not respond to current immunotherapy
drugs and among those that
initially respond, many become resistant
to the drugs' effects. Thus, besides developing
more effective immunotherapies,
doctors need to be able to determine
which patients respond well at the start
of treatments and, which ones keep or
stop responding in order to make the best
treatment decisions.
Because cancerous skin lesions of melanoma
patients are easily accessible, an
effective way to eradicate them could
be to apply immunotherapies locally, instead
of systemically infusing them into
the blood circulation. Also, monitoring
the immune system's reaction to the therapy
right at the tumor site, by sensitively
and continuously measuring different
biomarkers that signal the intended immune
cell activation and a desirable inflammatory
response, could enable better
and more personalized patient care.
Now, a research team at the Wyss Institute
at Harvard University, MIT, and Brigham
and Women's Hospital in Boston has developed
a new approach that integrates
a minimally invasive, painless microneedle
platform capable of absorbing the
cell-surrounding, biomarker-containing
fluid from deeper layers of the skin with
an ultra-sensitive, single-molecule detection
method (Simoa) that detects often
rare, yet relevant biomarkers with higher
sensitivity than conventional methods.
The researchers provided proof-of-concept
for their approach in a mouse melanoma
model in which they treated cancerous
lesions with a novel therapy. The
therapy acts locally on tumor lesions in
that it combines non-invasive focused ultrasound
(FUS), which generates heat at
the tumor site to instantly kill tumor cells,
Medical Design Briefs, January 2024
A new study demonstrates how biomarker molecules can be sampled from melanoma lesions using microneedles,
and measured with ultra-sensitive, single-molecule Simoa assays. (Credit: Wiley Editing Services)
with the delivery of a previously developed
nanoparticle-bound activator of an
inflammation-inducing protein known as
stimulator of interferon genes (STING).
The findings are reported in Advanced
Functional Materials.
" Rapid readout of the responses to
melanoma therapy using microneedles
may enable effective drug screening and
patient stratification to maximize therapeutic
benefits, " says Wyss Associate Faculty
member Natalie Artzi, PhD, who led
the study. Artzi is also an associate professor
of Medicine at Harvard Medical
School (HMS) and a Principal Research
Scientist at the Institute for Medical Engineering
and Science at MIT.
Artzi and her group first developed a
locally applied immunotherapy for melawww.medicaldesignbriefs.com
noma
that leveraged some of their previously
pioneered methods and expertise.
In a recent publication, which built on
the known fact that activation of the
inflammation-inducing STING protein
contributes to tumor cell killing, they
reported a significantly more effective
way to activate the protein in immune
cells. Natural activators (agonists) of
STING are not sufficiently stable in the
body and need to be given in high doses
that also can produce side effects. The
group's solution was to deliver multiple
copies of a synthetic STING agonist,
called a synthetic cyclic dinucleotide
(CDN), via nanoparticles (NP) that easily
traverse the plasma membrane and,
with the help of an engineered enzymatic
reaction, release their cargo inside
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Medical Design Briefs - January 2024

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