Eat 'em up: Next-generation therapeutic helps immune cells detect, destroy cancer: Supramolecule provides a double whammy to knock out cancer's 'eat-me-not' signaling, keep macrophages on the attack -- ScienceDaily

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Investigators have developed a therapeutic that delivers a double whammy to knock out both mechanisms." id="metasummary"/> <meta name="keywords" content="Cancer; Breast Cancer; Lung Cancer; Lymphoma; Brain Tumor; Skin Cancer; Prostate Cancer; Colon Cancer" id="metakeywords"/> <meta name="last-modified" content="Tue, 03 Jul 2018 04:16:01 GMT"/> <meta name="expires" content="Tue, 03 Jul 2018 08:16:01 GMT"/> <meta property="og:title" id="og_title" content="Eat 'em up: Next-generation therapeutic helps immune cells detect, destroy cancer: Supramolecule provides a double whammy to knock out cancer's 'eat-me-not' signaling, keep macrophages on the attack"/> <meta property="og:type" content="article"/> <meta property="og:url" id="og_url" content="https://web.archive.org/web/20180703055321/https://www.sciencedaily.com/releases/2018/07/180702111158.htm"/> <meta property="og:description" id="og_description" content="Researchers have found that cancer cells evade destruction by macrophages in two ways -- by converting cells to become docile, M2 macrophages, and by sending out an 'eat me not' signal that tricks M1 macrophages into letting them be. 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Investigators have developed a therapeutic that delivers a double whammy to knock out both mechanisms. </dd> <dt class="no-print">Share:</dt> <dd class="no-print"> <div id="share_top"> <div data-url="https://web.archive.org/web/20180703055321oe_/https://www.sciencedaily.com/releases/2018/07/180702111158.htm" class="ssk-sm ssk-group"> <a class="ssk ssk-icon ssk-facebook"></a> <a class="ssk ssk-icon ssk-twitter"></a> <a class="ssk ssk-icon ssk-google-plus"></a> <a class="ssk ssk-icon ssk-pinterest"></a> <a class="ssk ssk-icon ssk-linkedin"></a> <a class="ssk ssk-icon ssk-email"></a> </div> </div> </dd> </dl> <div class="row"> <div class="col-md-8 col-md-push-4"> <div class="fullstory">FULL STORY</div> <hr class="hr-fullstory"/>  <div class="clearfix"></div> <div id="story_text" class="hyphenate less-top-margin"> <p id="first" class="lead">Macrophages -- immune cells that engulf and digest particles and pathogens -- provide a first line of defense against bacteria and viruses and can also help destroy cancer cells. Macrophages play a paradoxical role, with M1 macrophages rousing the immune system to action and M2 macrophages quelling inflammation. Researchers have found that cancer cells evade destruction by macrophages in two ways -- by converting cells to become docile, M2 macrophages, and by sending out an "eat me not" signal that tricks M1 macrophages into letting them be. Investigators from Brigham and Women's Hospital have developed a therapeutic that delivers a double whammy to knock out both mechanisms. In preclinical models, the new approach has yielded promising results. The team's findings are published today in <em>Nature Biomedical Engineering</em>.</p> <div class="mobile-top-rectangle hidden-md hidden-lg"> <div class="textrule"> <span>advertisement</span> </div>  <div id="adslot-mobile-top-rectangle"> <script type="text/javascript"> googletag.cmd.push(function() { deployads.push(function() { deployads.gpt.display("adslot-mobile-top-rectangle") }); }); </script> </div> <hr class="hrrule"/> </div> <div id="text"> <p>"Clinicians are increasingly realizing that one drug or a one-size-fits-all approach is not enough when combatting cancer, and that a combination immunotherapy, such as blocking two distinct targets in the same immune cell, is the future of immuno-oncology. Our approach capitalizes on this concept," said co-corresponding author Ashish Kulkarni, PhD, a former instructor in the Division of Engineering in Medicine at BWH and assistant professor in the Department of Chemical Engineering at University of Massachusetts, Amherst.</p> <p>Kulkarni and colleagues have previously reported on the design and engineering of supramolecules -- therapeutics that are built from component molecules that click together like building blocks. To reinvigorate macrophages, the team designed a supramolecule that could block the "don't eat me" signal that cancer cells can produce and simultaneously inhibit signaling that converts macrophages to M2 subtype.</p> <p>The researchers tested the supramolecular therapeutic in animal models of aggressive forms of breast cancer and skin cancer, comparing their drug directly with a drug currently available in the clinic. Mice that were untreated formed large tumors by Day 10. Mice treated with currently available therapies showed decreased tumor growth. But mice treated with the new supramolecular therapy had complete inhibition of tumor growth. The team also reported an increase in survival and a significant reduction in metastatic nodes.</p> <p>"We can actually see macrophages eating cancer cells," said co-corresponding author Shiladitya Sengupta, PhD, BWH associate bioengineer and assistant professor of medicine at Harvard Medical School, citing confocal microscopy images published in the paper that show macrophages (red) engulfing cancer cells (green).</p> <p>The researchers plan to continue testing the new therapy in preclinical models to evaluate safety, efficacy and dosage. The supramolecular therapy they have designed has been licensed and they hope to move the therapeutic into clinical trials in the years ahead should preclinical testing continue to show promise.</p> <p>Funding for this work was provided by a Department of Defense Breakthrough Award (BC132168), an American Lung Association Innovation Award (LCD-259932-N), an NCI UO1 (CA214411), a National Cancer Institute of the National Institutes of Health (P50CA168504) and Hearst Foundation/Brigham and Women's Hospital Young Investigator Award.</p> </div> <div class="mobile-middle-rectangle hidden-md hidden-lg"> <div class="textrule"> <span>advertisement</span> </div>  <div id="adslot-mobile-middle-rectangle"> <script type="text/javascript"> googletag.cmd.push(function() { deployads.push(function() { deployads.gpt.display("adslot-mobile-middle-rectangle") }); }); </script> </div> <hr class="hrrule"/> </div> <hr class="hidden-sm hidden-xs"/> <div id="story_source"> <p><strong>Story Source:</strong></p> <p>Materials provided by <a href="https://web.archive.org/web/20180703055321/http://www.brighamandwomens.org/" rel="nofollow" target="_blank"><strong>Brigham and Women's Hospital</strong></a>. <em>Note: Content may be edited for style and length.</em></p> </div>  <hr/> <div id="journal_references"><p><strong>Journal Reference</strong>:</p> <ol class="journal"> <li>Ashish Kulkarni, Vineethkrishna Chandrasekar, Siva Kumar Natarajan, Anujan Ramesh, Prithvi Pandey, Jayashree Nirgud, Harshangda Bhatnagar, Driti Ashok, Amrendra Kumar Ajay, Shiladitya Sengupta. <strong>A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer</strong>. <em>Nature Biomedical Engineering</em>, 2018; DOI: <a href="https://web.archive.org/web/20180703055321/http://dx.doi.org/10.1038/s41551-018-0254-6" rel="nofollow" target="_blank">10.1038/s41551-018-0254-6</a> </li> </ol> <hr/> </div>  <div id="citations"> <div role="tabpanel" class="right-tabs clearfix"> <p class="pull-left"><strong>Cite This Page</strong>:</p>  <ul class="nav nav-tabs" role="tablist"> <li role="presentation" class="active"><a href="#citation_mla" aria-controls="citation_mla" role="tab" data-toggle="tab">MLA</a></li> <li role="presentation"><a href="#citation_apa" aria-controls="citation_apa" role="tab" data-toggle="tab">APA</a></li> <li role="presentation"><a href="#citation_chicago" aria-controls="citation_chicago" role="tab" data-toggle="tab">Chicago</a></li> </ul> <div class="tab-content tab-citations"> <div role="tabpanel" class="tab-pane active" id="citation_mla">Brigham and Women's Hospital. "Eat 'em up: Next-generation therapeutic helps immune cells detect, destroy cancer: Supramolecule provides a double whammy to knock out cancer's 'eat-me-not' signaling, keep macrophages on the attack." ScienceDaily. ScienceDaily, 2 July 2018. <www.sciencedaily.com/releases/2018/07/180702111158.htm>.</div> <div role="tabpanel" class="tab-pane" id="citation_apa">Brigham and Women's Hospital. (2018, July 2). Eat 'em up: Next-generation therapeutic helps immune cells detect, destroy cancer: Supramolecule provides a double whammy to knock out cancer's 'eat-me-not' signaling, keep macrophages on the attack. <em>ScienceDaily</em>. Retrieved July 3, 2018 from www.sciencedaily.com/releases/2018/07/180702111158.htm</div> <div role="tabpanel" class="tab-pane" id="citation_chicago">Brigham and Women's Hospital. "Eat 'em up: Next-generation therapeutic helps immune cells detect, destroy cancer: Supramolecule provides a double whammy to knock out cancer's 'eat-me-not' signaling, keep macrophages on the attack." 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Eat 'em up: Next-generation therapeutic helps immune cells detect, destroy cancer: Supramolecule provides a double whammy to knock out cancer's 'eat-me-not' signaling, keep macrophages on the attack -- ScienceDaily