tag:theconversation.com,2011:/institutions/university-of-chicago-pritzker-school-of-molecular-engineering-5602/articlesThe University of Chicago Pritzker School of Molecular Engineering2024-03-15T12:11:36Ztag:theconversation.com,2011:article/2243502024-03-15T12:11:36Z2024-03-15T12:11:36ZPacemaker powered by light eliminates need for batteries and allows the heart to function more naturally − new research<figure><img src="https://images.theconversation.com/files/580746/original/file-20240308-16-3gcx17.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists have designed a solar panel-like pacemaker that can precisely control heartbeats.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/female-silhouett-and-heart-with-pacemaker-royalty-free-image/1490726996">Eugene Mymrin/Moment via Getty Images</a></span></figcaption></figure><p>By harnessing light, my colleagues <a href="https://scholar.google.com.sg/citations?user=hO6bRlwAAAAJ&hl=en">and I</a> designed a wireless, ultrathin pacemaker that operates like a solar panel. This design not only eliminates the need for batteries but also minimizes disruptions to the heart’s natural function by molding to its contours. Our research, recently <a href="https://doi.org/10.1038/s41586-024-07016-9">published in the journal Nature</a>, offers a new approach to treatments that require electrical stimulation, such as heart pacing.</p>
<p><a href="https://theconversation.com/how-do-pacemakers-and-defibrillators-work-a-cardiologist-explains-how-they-interact-with-the-electrical-system-of-the-heart-217429">Pacemakers are medical devices</a> implanted in the body to regulate heart rhythms. They’re composed of electronic circuits with batteries and leads anchored to the heart muscle to stimulate it. However, leads can fail and damage tissue. The location of the leads can’t be changed once they’re implanted, limiting access to different heart regions. Because pacemakers use rigid, metallic electrodes, they may also damage tissue when <a href="https://www.nhlbi.nih.gov/health/heart-surgery/during">restarting the heart after surgery</a> or <a href="https://www.mayoclinic.org/diseases-conditions/heart-arrhythmia/symptoms-causes/syc-20350668">regulating arrhythmia</a>.</p>
<p>Our team envisioned a leadless and more flexible pacemaker that could precisely stimulate multiple areas of the heart. So we designed a device that <a href="https://doi.org/10.1038/s41586-024-07016-9">transforms light into bioelectricity</a>, or heart cell-generated electrical signals. Thinner than a human hair, our pacemaker is made of an optic fiber and silicon membrane that the <a href="https://tianlab.uchicago.edu/">Tian lab</a> and colleagues at the University of Chicago <a href="https://pme.uchicago.edu/">Pritzker School of Molecular Engineering</a> have spent years developing. </p>
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<figcaption><span class="caption">Like solar panels, this pacemaker is powered by light.</span></figcaption>
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<p>Unlike <a href="https://www.energy.gov/eere/solar/solar-photovoltaic-cell-basics">conventional solar cells</a> that are usually designed to collect as much energy as possible, we tweaked our device to generate electricity only at points where light strikes so it can precisely regulate heartbeats. We did this by using a layer of very small pores that can trap light and electrical current. Only cardiac muscles exposed to light-activated pores are stimulated.</p>
<p>Because our device is so small and light, it can be implanted without opening the chest. We were able to <a href="https://doi.org/10.1038/s41586-024-07016-9">successfully implant it</a> in the hearts of rodents and an adult pig, pacing the beats of different heart muscles. Because <a href="https://theconversation.com/organs-from-genetically-engineered-pigs-may-help-shorten-the-transplant-wait-list-175893">pig hearts</a> are anatomically similar to human hearts, this accomplishment shows our device’s potential to translate to people.</p>
<h2>Why it matters</h2>
<p>Heart disease is the <a href="https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death">leading cause of death around the world</a>. Annually, <a href="https://www.nhlbi.nih.gov/health/heart-surgery">over 2 million people</a> undergo open-heart surgery to treat heart problems, including to <a href="https://theconversation.com/how-do-pacemakers-and-defibrillators-work-a-cardiologist-explains-how-they-interact-with-the-electrical-system-of-the-heart-217429">implant devices</a> that regulate heart rhythms and prevent heart attacks.</p>
<p>Our ultralight device gently conforms to the surface of the heart, enabling less invasive stimulation and improved pacing and synchronized contraction. To reduce postoperative trauma and recovery time, our device can be implanted with a minimally invasive technique.</p>
<h2>What still isn’t known</h2>
<p>Currently, our technology is best first used for urgent heart conditions, including restarting the heart after surgery, heart attack and ventricular defibrillation. We continue to explore its long-term effects and durability in the human body.</p>
<p>The body’s internal environment is <a href="https://doi.org/10.1017/jfm.2022.272">rich in fluids</a> that are disturbed by the heart’s constant mechanical motion. This could potentially compromise the device’s functionality over time. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="ECG reading of patient with pacemaker syndrome" src="https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=303&fit=crop&dpr=1 600w, https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=303&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=303&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=380&fit=crop&dpr=1 754w, https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=380&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/580750/original/file-20240308-28-ptbgx3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=380&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Pacemaker syndrome is a condition that develops from stimulating heart muscles in isolation.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:E00031141_(CardioNetworks_ECGpedia).jpg">Michael Rosengarten BEng, MD.McGill/EKG World Encyclopedia via Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Moreover, researchers don’t fully understand how the body reacts to prolonged exposure to medical devices. The formation of <a href="https://theconversation.com/implants-like-pacemakers-and-insulin-pumps-often-fail-because-of-immune-attacks-stopping-them-could-make-medical-devices-safer-and-longer-lasting-211090">scar tissue</a> around the device after implantation can diminish its sensitivity. We are developing special surface treatments and biomaterial coatings to decrease the likelihood of rejection. </p>
<p>Although the breakdown of our device results in a nontoxic substance the body can safely absorb called <a href="https://doi.org/10.1038/s41578-020-0230-0">silicic acid</a>, evaluating how the body responds to extended implantation is essential to ensure safety and effectiveness.</p>
<h2>What’s next</h2>
<p>To achieve long-term implantation and tailor the device to each patient, we are refining the rate at which it dissolves naturally in the body. We are exploring enhancements to make the device compatible as a wearable pacemaker. This involves integrating a wireless light-emitting diode, or LED, beneath the skin that is connected to the device via an optical fiber.</p>
<p>Our ultimate goal is to broaden the scope of what we call photoelectroceuticals beyond cardiac care. This includes <a href="https://theconversation.com/brain-stimulation-can-rewire-and-heal-damaged-neural-connections-but-it-isnt-clear-how-research-suggests-personalization-may-be-key-to-more-effective-therapies-182491">neurostimulation</a>, neuroprostheses and pain management to treat neurodegenerative conditions such as <a href="https://www.parkinson.org/understanding-parkinsons/statistics">Parkinson’s disease</a>. </p>
<p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take on interesting academic work.</em></p><img src="https://counter.theconversation.com/content/224350/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Pengju Li consults to the Pritzker School of Molecular Engineering. He receives funding from the University of Chicago.</span></em></p>Researchers designed an ultrathin pacemaker that can be implanted via minimally invasive techniques, potentially improving recovery time and reducing the risk of complications.Pengju Li, Ph.D. Candidate in Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2079742023-07-05T12:23:21Z2023-07-05T12:23:21ZHow splitting sound might lead to a new kind of quantum computer<p>When you turn on a lamp to brighten a room, you are experiencing light energy transmitted as photons, which are small, discrete quantum packets of energy. These photons must obey the sometimes strange laws of quantum mechanics, which, for instance, dictate that photons are indivisible, but at the same time, allow a photon <a href="https://www.cambridge.org/highereducation/books/introduction-to-quantum-mechanics/990799CA07A83FC5312402AF6860311E#overview">to be in two places at once</a>. </p>
<p>Similar to the photons that make up beams of light, indivisible quantum particles <a href="https://news.mit.edu/2010/explained-phonons-0706">called phonons</a> make up a beam of sound. These particles emerge from the collective motion of quadrillions of atoms, much as a “stadium wave” in a sports arena is due to the motion of thousands of individual fans. When you listen to a song, you’re hearing a stream of these very small quantum particles.</p>
<p>Originally conceived to <a href="https://www.wiley.com/en-us/Introduction+to+Solid+State+Physics%2C+8th+Edition-p-9780471415268">explain the heat capacities of solids</a>, phonons are predicted to obey the same rules of quantum mechanics as photons. The technology to generate and detect individual phonons has, however, lagged behind that for photons. </p>
<p>That technology is only now being developed, in part by <a href="https://clelandlab.uchicago.edu/">my research group</a> at the Pritzker School of Molecular Engineering at the University of Chicago. <a href="https://scholar.google.com/citations?user=uE04v0gAAAAJ&hl=en&oi=ao">We are exploring</a> the fundamental quantum properties of sound by splitting phonons in half and entangling them together.</p>
<p>My group’s fundamental research on phonons may one day allow researchers to build a new type of quantum computer, called a mechanical quantum computer.</p>
<h2>Splitting sound with ‘bad’ mirrors</h2>
<p>To explore the quantum properties of phonons, our team uses acoustic mirrors, which can direct beams of sound. Our latest experiments, published in <a href="https://doi.org/10.1126/science.adg8715">a recent issue of Science</a>, however, involve “bad” mirrors, called beam splitters, that reflect about half the sound sent toward them and let the other half through. Our team decided to explore what happens when we direct a phonon at a beam splitter. </p>
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<a href="https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diagram showing a line representing a beam splitter, which a phonon hits. Two dashed lines on either side of the beam splitter line demarcate that the phonon is both reflected off the beam splitter and transmitted to the other side, in superposition." src="https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534146/original/file-20230626-29-lr358i.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A beam splitter for phonons – the phonon enters a superposition state where it is both reflected and transmitted until it is detected.</span>
<span class="attribution"><span class="source">A.N. Cleland</span></span>
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</figure>
<p>As a phonon is indivisible; it cannot be split. Instead, after interacting with the beam splitter, the phonon ends up in what is called a “<a href="https://scienceexchange.caltech.edu/topics/quantum-science-explained/quantum-superposition">superposition state</a>.” In this state the phonon is, somewhat paradoxically, both reflected and transmitted, and you’re equally likely to detect the phonon in either state. If you intervene and detect the phonon, half the time you will measure that it was reflected and half the time that it was transmitted; in a sense, the state is <a href="https://doi.org/10.1119/1.3243279">selected at random</a> by the detector. Absent the detection process, the phonon will remain in the superposition state of being both transmitted and reflected. </p>
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<figcaption><span class="caption">A brief Ted-Ed explainer on superposition, which happens when particles can exist in multiple places at once.</span></figcaption>
</figure>
<p>This superposition effect was observed many years ago with photons. Our results indicate that phonons have the same property. </p>
<h2>Entangled phonons</h2>
<p>After demonstrating that phonons can go into quantum superpositions just as photons do, my team asked <a href="https://doi.org/10.1126/science.adg8715">a more complex question</a>. We wanted to know what would happen if we sent two identical phonons into the beam splitter, one from each direction. </p>
<p>It turns out that each phonon will go into a similar superposition state of half-transmitted and half-reflected. But because of the physics of the beam splitter, if we time the phonons precisely, they will quantum-mechanically interfere with one another. What emerges is actually a superposition state of two phonons going one way and two phonons going the other – the two phonons are thus <a href="https://scienceexchange.caltech.edu/topics/quantum-science-explained/entanglement">quantum-mechanically entangled</a>. </p>
<p>In quantum entanglement, each phonon is in a superposition of reflected and transmitted, but the two phonons are locked together. This means detecting one phonon as having been transmitted or reflected forces the other phonon to be in the same state.</p>
<p>So, if you detect, you’ll always detect two phonons, going one way or the other, never one phonon going each way. This same effect for light, the combination of superposition and interference of two photons, is called the <a href="https://doi.org/10.1103/PhysRevLett.59.2044">Hong-Ou-Mandel effect</a>, after the three physicists who first predicted and observed it in 1987. Now, my group has demonstrated this effect with sound. </p>
<h2>The future of quantum computing</h2>
<p>These results suggest that it may now be possible to build a mechanical quantum computer using phonons. There are continuing efforts to build <a href="https://news.mit.edu/2020/explained-quantum-engineering-1210">optical quantum computers</a> that require only the emission, detection and interference of single photons. These are in parallel with efforts to build electrical quantum computers, which through the use of large numbers of entangled particles promise an exponential speedup for certain problems, such as factoring large numbers or simulating quantum systems.</p>
<p>A quantum computer using phonons could be very compact and self-contained, built entirely on a chip similar to that of a laptop computer’s processor. Its small size could make it easier to implement and use, if researchers can further expand and improve phonon-based technologies.</p>
<p>My group’s <a href="https://doi.org/10.1126/science.adg8715">experiments with phonons</a> use qubits – the same technology that powers electronic quantum computers – which means that as the technology for phonons catches up, there’s the potential to integrate phonon-based computers with electronic quantum computers. Doing so could yield new, potentially unique computational abilities.</p><img src="https://counter.theconversation.com/content/207974/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew N. Cleland receives funding from various US federal funding agencies. He is a fellow of the American Physical Society (APS) and the American Association for the Advancement of Science. He is currently Past Chair of the Division of Quantum Information of the APS, and in 2023 held a Fulbright Distinguished Chair. He is a founder and a board member of Spectradyne LLC, a startup company based in Los Angeles that is commercializing electrical and optical detection of nanoparticles in fluids.</span></em></p>Scientists show they can create quantum superpositions of sound particles, pointing to the potential for mechanical quantum computers.Andrew N. Cleland, Professor of Molecular Engineering Innovation and Enterprise, University of Chicago Pritzker School of Molecular EngineeringLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1991382023-02-05T16:53:53Z2023-02-05T16:53:53ZCancer : les thérapies de différenciation, ou comment faire revenir les cellules cancéreuses dans le droit chemin<figure><img src="https://images.theconversation.com/files/508192/original/file-20230205-15-3bqf1z.jpg?ixlib=rb-1.1.0&rect=383%2C398%2C1171%2C1073&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cette image de microscopie montre des cellules cancéreuses du pancréas en croissance (noyau en bleu, membranes en rouge). </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/26645788710/">Min Yu/Eli et Edythe Broad Center for Regenerative Medicine and Stem Cell Research, USC / NIH / Flickr</a></span></figcaption></figure><p>Les scientifiques ont baptisé de telles cellules, « cellules souches cancéreuses ». Ils <a href="https://doi.org/10.1186/s13578-017-0188-9">pensent qu’elles ont une part de resposabilité</a> non seulement dan l’initiation des cancers, mais aussi dans leur progression, le développement de métastases, les récidives et la résistance aux traitements.</p>
<h2>Qu’est-ce que la thérapie de différenciation ?</h2>
<p>Un nombre croissant de preuves semble indiquer que les cellules souches cancéreuses sont capables de ce différencier en de multiples types cellulaires, y compris des cellules non cancéreuses. Forts de ce constat, les chercheurs ont eu l’idée d’essayer de mettre au point un nouveau type de traitement, appelé <a href="https://doi.org/10.1177/1010428317729933">thérapies de différenciation</a>. </p>
<p>Le concept a été forgé suite aux observations qui ont révélé que les hormones et les cytokines, deux types de protéines qui jouent un rôle clé dans la communication entre les cellules, pouvaient <a href="https://doi.org/10.1038/nrc.2017.103">stimuler la maturation des cellules souches et ce faisant, leur faire perdre leur capacité de régénération</a>. Réussir à forcer les cellules souches cancéreuses à se différencier en des cellules plus « matures » pourrait donc stopper leur prolifération incontrôlable, et en faire des cellules normales. </p>
<p>La thérapie de différenciation a déjà fait ses preuves dans le traitement de la <a href="https://doi.org/10.1182/blood-2009-01-198911">leucémie aiguë promyélocytaire</a>, un <a href="https://www.santepubliquefrance.fr/docs/survie-des-personnes-atteintes-de-cancer-en-france-metropolitaine-1989-2018-leucemie-aigue-myeloide-promyelocytaire">cancer des cellules sanguines agressif</a>. Dans le cas de cette maladie, l’<a href="https://www.academie-medecine.fr/le-dictionnaire/index.php?q=acide%20r%C3%A9tino%C3%AFque">acide rétinoïque</a> et l’arsenic sont utilisés pour bloquer une protéine qui empêche les cellules myéloïdes, un type de cellules sanguines dérivées de cellules de la moelle osseuse, de poursuivre leur maturation. En leur permettant de poursuivre leur développement normal, ce traitement leur fait perdre leurs caractéristiques cancéreuses.</p>
<p>Autre intérêt des thérapies de différenciation : puisqu’elles ne se focalisent pas sur la destruction des cellules cancéreuses et ne nécessitent pas de soumettre les cellules saines à proximité à des produits chimiques toxiques, elles peuvent s’avérer <a href="https://doi.org/10.1182%2Fblood-2009-01-198911">moins délétères que les traitements traditionnels</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Image en microscopie de leucémie aiguë promyélocytaire " src="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">La leucémie aiguë promyélocytaire peut être traitée par thérapie de différenciation.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/acute-promyelocytic-leukemia-cells-royalty-free-image/1417347912">jarun011/iStock via Getty Images Plus</a></span>
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</figure>
<h2>Utiliser les cellules souches pour traiter le cancer</h2>
<p>Il existe plusieurs autres pistes potentielles mettant à contribution les cellules souches pour lutter contre le cancer. Les cellules souches cancéreuses peuvent par exemple être <a href="https://doi.org/10.1038/s41392-020-0110-5">directement ciblées</a> dans l’optique de stopper leur croissance, ou bien être transformées en <a href="https://doi.org/10.1515/iss-2016-0005">« chevaux de Troie »</a> capables de s’attaquer aux autres cellules tumorales.</p>
<p><a href="https://doi.org/10.1155/2016/1740936">Les cellules souches cancéreuses quiescentes</a>, qui ne se divisent pas, mais demeurent vivantes, sont elles aussi de potentielles cibles thérapeutiques. Ces cellules jouent un rôle important dans l’émergence de résistance aux traitements dans une grande variété de sortes de cancers, car elles ont une capacité de régénération et de survie encore plus importante que celle des autres cellules souches cancéreuses.
Leur quiescence peut persister durant des décennies, ce qui signifie qu’elles peuvent être à l’origine de récidives de la maladie. Elles sont malheureusement difficiles à distinguer des cellules souches cancéreuses « classiques », ce qui complique leur étude. </p>
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<p>Autre piste suivie par les chercheurs : modifier génétiquement des cellules souches afin qu’elles expriment une protéine capable de le lier spécifiquement à une cible spécifique, présente dans des cellules cancéreuses. Cette approche permet d’augmenter l’efficacité des traitements, en relâchant les médicaments directement dans la tumeur. Les <a href="https://doi.org/10.3389%2Ffbioe.2020.00043">cellules souches mésenchymateuses</a> provenant de la moelle osseuse sont par exemple capables de migrer naturellement vers les tumeurs, et de s’y arrimer. Elles pourraient donc être utilisées pour délivrer des molécules thérapeutiques directement au contact des cellules cancéreuses.</p>
<p>Les cellules souches peuvent aussi être utilisées pour produire des <a href="https://doi.org/10.1002/wdev.399">organoïdes modèles</a>, qui sont des sortes de versions miniatures des organes, afin de tester de potentiels médicaments anticancéreux et d’étudier les mécanismes qui mènent à la maladie</p>
<h2>Les défis des thérapies à base de cellules souches</h2>
<p>Bien que les nombreux avantages des cellules souches suscitent de nombreux intérêts chez les scientifiques qui développent des thérapies destinées à traiter le cancer, <a href="https://doi.org/10.18632%2Foncotarget.20798">plusieurs défis restent encore à relever</a>. On sait par exemple que bon nombre des thérapies à base de cellule souche actuelles sont incapables d’éliminer à elle seule les tumeurs : elles doivent être pour cela conjuguées à d’autres médicaments. </p>
<p>Il existe également des préoccupations concernant la capacité éventuelle des cellules souches à promouvoir la croissance tumorale.</p>
<p>En dépit de ces obstacles, selon nous, les technologies à base de cellules souches ont le potentiel d’ouvrir de nouvelles perspectives dans le domaine des thérapies anticancéreuses. La conjugaison du génie génétique et des cellules souches semble en mesure de surmonter les principaux inconvénients posés par les chimiothérapies actuelles, notamment la question de leur toxicité pour les cellules saines. Si nous poursuivons les recherches, il se pourrait que les thérapies ciblant les cellules souches cancéreuses finissent un jour par faire partie des traitements standards d’un grand nombre de type de cancers.</p><img src="https://counter.theconversation.com/content/199138/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Les auteurs ne travaillent pas, ne conseillent pas, ne possèdent pas de parts, ne reçoivent pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'ont déclaré aucune autre affiliation que leur organisme de recherche.</span></em></p>De nombreuses tumeurs contiennent des cellules souches cancéreuses qui les aident à se développer et à échapper aux traitements. Une nouvelle piste tente de rendre ces cellules à nouveau normales.Huanhuan Joyce Chen, Assistant Professor of Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringAbhimanyu Thakur, Postdoctoral Scholar in Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1915592023-01-11T13:25:40Z2023-01-11T13:25:40ZTriggering cancer cells to become normal cells – how stem cell therapies can provide new ways to stop tumors from spreading or growing back<figure><img src="https://images.theconversation.com/files/503356/original/file-20230105-19-bvp86r.jpg?ixlib=rb-1.1.0&rect=6%2C6%2C2038%2C2038&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This image shows pancreatic cancer cells (blue) growing, encased within membranes (red).</span> <span class="attribution"><a class="source" href="https://flic.kr/p/GAACEb">Min Yu/Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC via NIH/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>How cells <a href="https://doi.org/10.3390%2Fijms21186489">become cancerous</a> is a process researchers are still trying to fully understand. Generally, normal cells grow and multiply through controlled cell division, where <a href="https://doi.org/10.3389/fcell.2021.645593">old and damaged cells</a> are replaced after they die by new cells. Sometimes this process stops working, leading cells to start growing uncontrollably and develop into a tumor.</p>
<p>Traditionally, cancer treatments like chemotherapy, immunotherapy, radiation and surgery focus on killing cancer cells. Another type of treatment using stem cells called <a href="https://doi.org/10.1177/1010428317729933">differentiation therapy</a>, however, focuses on persuading cancer cells to become normal cells. </p>
<p><a href="https://scholar.google.com/citations?user=GNSivG8AAAAJ&hl=en">We are</a> <a href="https://chen.uchicago.edu/abhimanyu-thakur-ph-d/">researchers</a> who study how stem cells, or immature cells that can develop into different types of cells, behave in states of health and disease. We believe that stem cells can provide potential treatments for cancer of all types in many different ways.</p>
<h2>How do stem cells contribute to cancer?</h2>
<p><a href="https://www.the-scientist.com/university/brush-up-what-is-stemness-and-pluripotency-70571">Stem cells</a> are unspecialized cells, meaning they can eventually become any one of the various types of cells that make up different parts of the body. They can replenish cells in the skin, bone, blood and other organs during development, and regenerate and repair tissues when they’re damaged.</p>
<p>There are different types of stem cells. Embryonic stem cells are the first cells that initially form after a sperm fertilizes an egg, and can give rise to all other cell types in the human body. Adult stem cells are more mature, meaning they can replace damaged cells only in one type of organ and have a limited ability to multiply. Researchers can <a href="https://doi.org/10.1007%2Fs13238-021-00863-6">reprogram adult stem cells, or differentiated cells</a>, in the lab to act like embryonic stem cells.</p>
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<figcaption><span class="caption">Cells become specialized over the course of development.</span></figcaption>
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<p>Because stem cells can survive longer than regular cells, they have a much higher probability of accumulating genetic mutations that can result in loss of control over their growth and ability to regenerate. This is why many tumors harbor a small subpopulation of cells that <a href="https://doi.org/10.1038%2Flabinvest.2008.14">function like stem cells</a>. These so-called cancer stem cells are <a href="https://doi.org/10.1186/s13578-017-0188-9">thought to be responsible</a> at least in part for cancer initiation, progression, metastasis, recurrence and treatment resistance.</p>
<h2>What is differentiation therapy?</h2>
<p>Accumulating evidence is also showing that cancer stem cells can differentiate into multiple cell types, including noncancerous cells. Researchers are taking advantage of this fact through a type of treatment called <a href="https://doi.org/10.1177/1010428317729933">differentiation therapy</a>. </p>
<p>The concept of differentiation therapy <a href="https://doi.org/10.1038/nrc.2017.103">originated from scientists observing</a> that hormones and cytokines, which are proteins that play a key role in cell communication, can stimulate stem cells to mature and lose their ability to regenerate. It followed that forcing cancer stem cells to differentiate into more mature cells could subsequently stop them from multiplying uncontrollably, making them become normal cells.</p>
<p>Differentiation therapy has been successful in treating <a href="https://doi.org/10.1182/blood-2009-01-198911">acute promyelocytic leukemia</a>, an aggressive blood cancer. In this case, retinoic acid and arsenic are used to block a protein that stops myeloid cells, a type of blood cell derived from the bone marrow, from fully maturing. By allowing these cells to fully mature, they lose their cancerous qualities.</p>
<p>Furthermore, because differentiation therapy doesn’t focus on killing cancer cells and doesn’t surround healthy cells in the body with harmful chemicals, it can be <a href="https://doi.org/10.1182%2Fblood-2009-01-198911">less toxic</a> than traditional treatments.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of acute promyelocytic leukemia" src="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503362/original/file-20230105-22-8a0umi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Acute promyelocytic leukemia, as shown in this microscopy image, can be treated with differentiation therapy.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/acute-promyelocytic-leukemia-cells-royalty-free-image/1417347912">jarun011/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<h2>Using stem cells to treat cancer</h2>
<p>There are many other potential ways to use stem cells to treat cancer. For example, cancer stem cells can be <a href="https://doi.org/10.1038/s41392-020-0110-5">directly targeted</a> to stop their growth, or turned into “<a href="https://doi.org/10.1515/iss-2016-0005">Trojan horses</a>” that attack other tumor cells.</p>
<p><a href="https://doi.org/10.1155/2016/1740936">Quiescent cancer stem cells</a>, which don’t divide but are still alive, are another potential drug target. These cells typically play a big role in treatment resistance for various cancer types because they are able to regenerate and avoid death even better than regular cancer stem cells. Their quiescent quality can persist for decades and lead to a cancer relapse. They are also challenging to distinguish from regular cancer stem cells, making them difficult to study.</p>
<p>Researchers can also genetically engineer stem cells to express a protein that binds to a desired target in a cancer cell, increasing the efficacy of treatments by releasing drugs right at the tumor. For example, <a href="https://doi.org/10.3389%2Ffbioe.2020.00043">mesenchymal stem cells</a> derived from bone marrow naturally migrate toward and stick to tumors, and can be used to deliver cancer drugs directly to cancer cells.</p>
<p>Stem cells can also be used to make <a href="https://doi.org/10.1002/wdev.399">organoid models</a>, or miniature versions of organs, to screen potential cancer drugs and study the underlying mechanisms that lead to cancer. </p>
<h2>Challenges in stem cell therapy</h2>
<p>Although, stem cells hold numerous advantages in their use in cancer therapy, they also <a href="https://doi.org/10.18632%2Foncotarget.20798">face various challenges</a>. For example, many current stem cell therapies that aren’t used in combination with other drugs are unable to completely eliminate tumors. There are also concerns about stem cell therapies potentially promoting tumor growth.</p>
<p>Despite these challenges, we believe that stem cell technologies have the potential to open new avenues for cancer therapy. Integrating genetic engineering with stem cells can overcome the major drawbacks of chemotherapeutics, such as toxicity to healthy cells. With further research, cancer stem cell therapies may one day become part of the standard of care for many types of cancer.</p><img src="https://counter.theconversation.com/content/191559/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many tumors have cancer stem cells that help them grow and evade treatments. Differentiation therapy forces these cells to mature, stopping growth with less toxicity than traditional treatments.Huanhuan Joyce Chen, Assistant Professor of Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringAbhimanyu Thakur, Postdoctoral Scholar in Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1898602022-11-17T13:28:13Z2022-11-17T13:28:13ZFlexible AI computer chips promise wearable health monitors that protect privacy<figure><img src="https://images.theconversation.com/files/494521/original/file-20221109-2910-hpmo70.JPG?ixlib=rb-1.1.0&rect=0%2C3%2C1125%2C626&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A device like this could one day monitor and assess your health.</span> <span class="attribution"><span class="source">Sihong Wang Research Group/University of Chicago</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em> </p>
<h2>The big idea</h2>
<p>My colleagues and <a href="https://scholar.google.com/citations?user=9xDIug8AAAAJ&hl=en">I</a> have developed a flexible, stretchable electronic device that runs machine-learning algorithms to continuously collect and analyze health data directly on the body. The skinlike sticker, developed <a href="https://wanglab.uchicago.edu/">in my lab</a> at the University of Chicago’s Pritzker School of Molecular Engineering, includes a soft, stretchable computing chip that mimics the human brain. </p>
<p>To create this type of device, we turned to electrically conductive polymers that have been used to build semiconductors and transistors. These polymers are made to be stretchable, like a rubber band. Rather than working like a typical computer chip, though, the chip we’re working with, called a neuromorphic computing chip, functions more like a human brain. It’s able to both store and analyze data.</p>
<p>To test the usefulness of the new device, my colleagues and I used it to analyze electrocardiogram data representing the electrical activity of the human heart. We trained the device to classify ECGs into five categories: healthy and four types of abnormal signals. Even in conditions where the device is repeatedly stretched by movements of the wearer’s body, the device <a href="https://doi.org/10.1016/j.matt.2022.07.016">could still accurately classify the heartbeats</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a small rectangle of clear rubber being stretched between two hands we face in the background" src="https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=378&fit=crop&dpr=1 600w, https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=378&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=378&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=475&fit=crop&dpr=1 754w, https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=475&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/494503/original/file-20221109-13740-snz30g.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=475&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">These electronic circuits are flexible and stretchable.</span>
<span class="attribution"><span class="source">UChicago Pritzker Molecular Engineering/John Zich</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Why it matters</h2>
<p>Most of the signals from the human body, such as the electrical activity in the heart recorded by ECG, are typically weak and subtle. Accurately recording these small signals requires direct contact between electronic devices and the human body. This can only be achieved by fabricating electronic devices to be as soft and stretchy as skin. We envision that wearable electronics will play a key role in tracking complex indicators of human health, including body temperature, cardiac activity, levels of oxygen, sugar, metabolites and immune molecules in the blood. </p>
<p>Analyzing large amounts of continuously acquired health data is challenging, however. A single piece of data must be put into the broader perspective of a patient’s full health history, and that is a big task. Cutting-edge machine-learning algorithms that identify patterns in extremely complex data sets are the most promising route to being able to pick out the most important signals of disease. </p>
<p>A typical approach to using machine learning to analyze real-time health data is to transmit the data wirelessly from wearable devices to a computer. But this poses challenges. Sending health data wirelessly is not only slow and consumes extra power, but it also raises privacy concerns. Our research aims to make the AI analysis of health data happen within these skinlike wearable devices, which would minimize the amount of information a device would need to transmit. </p>
<p>The ultimate goal is for this on-the-spot analysis to be able to send patients or health care providers timely alerts, or even one day automatically adjust medication dispensed by other wearable or implanted devices.</p>
<h2>What other research is being done</h2>
<p>Other research about AI processing health data collected from wearable devices has mainly involved transferring the data to computers running AI algorithms. These projects have demonstrated the potential of AI for <a href="https://doi.org/10.1002/adma.202104178">extracting useful information</a> from complicated health data.</p>
<p>The recent development of <a href="https://doi.org/10.1038/nmat4856">flexible neuromorphic processors</a> is an important step toward running AI data analysis directly on wearable devices, but these flexible processors lack skinlike stretchability and softness, which makes it difficult to build them into wearable devices. In contrast, our device has the skinlike properties necessary for a wearable health monitor.</p>
<h2>What’s next</h2>
<p>Moving forward, researchers are likely to extend this type of AI analysis integrated in wearable devices to other types of health conditions and diseases. My lab is planning to improve our device, both to better integrate the device’s components and expand the types of machine-learning algorithms it can be used with.</p>
<p>Our work is a good starting point for creating devices that build artificial intelligence into wearable electronics – devices that could help people live longer and healthier lives.</p><img src="https://counter.theconversation.com/content/189860/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sihong Wang receives funding from the Office of Naval Research, National Science Foundation, and National Institute of Health. He has submitted a patent application for the technology described in this article.</span></em></p>A type of computer chip that mimics both the skin and brain could pave the way for wearable devices that monitor and analyze health data using AI right on the body.Sihong Wang, Assistant Professor of Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1835882022-06-01T12:14:37Z2022-06-01T12:14:37Z‘Masked’ cancer drug stealthily trains immune system to kill tumors while sparing healthy tissues, reducing treatment side effects<figure><img src="https://images.theconversation.com/files/466370/original/file-20220531-14-t0h7ly.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2048%2C2048&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Dendritic cells (green) produce cytokines like IL-12, which can train T cells (pink) to attack tumors.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/JRzxEb">Victor Segura Ibarra and Rita Serda/National Cancer Institute via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Many cancer treatments are notoriously savage on the body. Drugs often attack both healthy cells and tumor cells, causing a plethora of side effects. <a href="https://www.cancer.gov/about-cancer/treatment/types/immunotherapy">Immunotherapies</a> that help the immune system recognize and attack cancer cells are no different. Though they have <a href="https://doi.org/10.1001/jamanetworkopen.2019.2535">prolonged the lives of countless patients</a>, they work in only a subset of patients. One study found that <a href="https://doi.org/10.3389/fonc.2020.600573">fewer than 30% of breast cancer patients</a> respond to one of the most common forms of immunotherapy. </p>
<p>But what if drugs could be engineered to attack only tumor cells and spare the rest of the body? To that end, <a href="https://pme.uchicago.edu/group/hubbell-lab">my colleagues</a> <a href="https://scholar.google.com/citations?user=7KTLoToAAAAJ&hl=en&oi=ao">and I</a> at the University of Chicago’s <a href="https://pme.uchicago.edu/">Pritzker School of Molecular Engineering</a> have <a href="https://doi.org/10.1038/s41551-022-00888-0">designed a method</a> to keep one promising cancer drug from wreaking havoc by “masking” it until it reaches a tumor.</p>
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<figcaption><span class="caption">Immunotherapies help the immune system recognize and target cancer cells.</span></figcaption>
</figure>
<h2>The promise of IL-12</h2>
<p><a href="https://doi.org/10.1038/s41416-018-0328-y">Cytokines</a> are proteins that can modulate how the immune system responds to threats. One way they do this is by activating <a href="https://doi.org/10.1038/nri819">killer T cells</a>, a type of white blood cells that can attack cancer cells. Because cytokines can train the immune system to kill tumors, this makes them very promising as cancer treatments.</p>
<p>One such cytokine is interleukin-12, or IL-12. Though it was <a href="https://doi.org/10.1084%2Fjem.2045fta">discovered more than 30 years ago</a>, IL-12 still isn’t an FDA-approved therapy for cancer patients because of its <a href="https://doi.org/10.1126/science.270.5238.908.a">severe side effects</a>, such as liver damage. This is in part because IL-12 instructs immune cells to produce a large amount of inflammatory molecules that can damage the body.</p>
<p>Scientists have since been working to reengineer IL-12 to be more tolerable while retaining its powerful cancer-killing effects.</p>
<h2>Masking the killer</h2>
<p>To create a safer version of IL-12, my colleagues and I took advantage of one of the main differences between healthy and cancerous tissue: an excess of growth-promoting enzymes in cancers. Because cancer cells proliferate very rapidly, they overproduce <a href="https://doi.org/10.1186/s12885-019-5768-0">certain enzymes</a> that help them invade the nearby healthy tissue and <a href="https://doi.org/10.1007/s002800051097">metastasize to other parts of the body</a>. Healthy cells grow at a much slower pace and produce fewer of these enzymes.</p>
<p>With this in mind, we “masked” IL-12 with a cap that covers the part of the molecule that normally binds to immune cells to activate them. The cap is removed only when it comes into contact with enzymes found in the vicinity of tumors. When these enzymes chop off the cap, IL-12 is reactivated and spurs nearby killer T cells to attack the tumor.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&rect=0%2C0%2C540%2C360&q=45&auto=format&w=1000&fit=clip"><img alt="Killer T cells surrounding a cancer cell" src="https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&rect=0%2C0%2C540%2C360&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/465808/original/file-20220527-13-galqhz.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Killer T cells (green and red) can attach to cancer cells (blue, center) and kill them by releasing toxic chemicals (red), a move scientists have dubbed ‘the kiss of death.’</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/xuSZkh">NIH/Flickr</a></span>
</figcaption>
</figure>
<p>When we applied these masked IL-12 molecules to both healthy and tumor tissue donated by melanoma and breast cancer patients, our results confirmed that only the tumor samples were able to remove the cap. This indicated that masked IL-12 could potentially drive a strong immune response against tumors without causing damage to healthy organs.</p>
<p>We then examined how safe masked IL-12 is by measuring <a href="https://www.mayoclinic.org/tests-procedures/liver-function-tests/about/pac-20394595">liver damage biomarkers</a> in mice. We found that immune-related side effects typically <a href="https://doi.org/10.1177%2F019262339902700112">associated with IL-12</a> were notably absent in mice treated with masked IL-12 over a period of several weeks, indicating improved safety.</p>
<p>In breast cancer models, our masked IL-12 resulted in a 90% cure rate, while treatment with a commonly used immunotherapy called a <a href="https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/immunotherapy/types/checkpoint-inhibitors">checkpoint inhibitor</a> resulted in only a 10% cure rate. In a model of colon cancer, masked IL-12 showed a 100% cure rate.</p>
<p>Our next step is to test the modified IL-12 in cancer patients. While it <a href="https://theconversation.com/from-the-research-lab-to-your-doctors-office-heres-what-happens-in-phase-1-2-3-drug-trials-138197">will take time</a> to bring this encouraging development directly to patients, we believe a promising new treatment is on the horizon.</p><img src="https://counter.theconversation.com/content/183588/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Aslan Mansurov consults to and owns shares in Arrow Immune Inc, which is developing the technology presented in the article. </span></em></p>One promising cancer treatment has been in the works for decades, but severe side effects have kept it out of the clinic. A reengineered version may offer a way to safely harness its potent effects.Aslan Mansurov, Postdoctoral Researcher in Molecular Engineering, University of Chicago Pritzker School of Molecular EngineeringLicensed as Creative Commons – attribution, no derivatives.