{"655929":{"#nid":"655929","#data":{"type":"news","title":"Scaffolding Tumor Formation Sets the Stage for Better Immunotherapies","body":[{"value":"\u003Cp\u003EThe discrepancy between preclinical advances in breast cancer immunotherapy and poor patient outcomes is rooted in the limitations of current breast cancer models. These models often fail to mimic complex interactions between cancer cells and key immune cells present in the tumor microenvironment.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EUtilizing a collaborative approach, Susan N. Thomas, associate professor in the \u003Ca href=\u0022https:\/\/www.me.gatech.edu\/\u0022\u003EGeorge W. Woodruff School of Mechanical Engineering\u003C\/a\u003E at the Georgia Institute of Technology, and former doctoral student Meghan O\u0026rsquo;Melia developed a novel way to generate breast tumor models faster, more reliably, and with dramatically less immune variability than existing models. Their innovative research, published in the January issue of \u003Ca href=\u0022https:\/\/onlinelibrary.wiley.com\/doi\/epdf\/10.1002\/adma.202108084\u0022\u003E\u003Cem\u003EAdvanced Materials\u003C\/em\u003E\u003C\/a\u003E, has the potential to revolutionize the development of immunotherapy treatments and can also help elucidate why patients with the same type of breast cancer respond differently to treatment.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EBy using a gel-like matrix as a scaffold to grow breast cancer tumors, Thomas and O\u0026rsquo;Melia were able to modulate how immune cells filter into a tumor\u0026rsquo;s microenvironment. In doing so, they created tumor models exceptionally well-suited to immunotherapy drug testing. Moreover, by tweaking the scaffold, they were able to replicate immune microenvironments seen in treatment-resistant breast cancer patients.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;This work provides us with new models to understand how tumor microenvironments influence responses to immunotherapies,\u0026rdquo; said O\u0026rsquo;Melia, now a postdoctoral fellow at Harvard. \u0026ldquo;We see potential for predicting, based on the immune characteristics of a patient\u0026rsquo;s tumor, what therapy that person will best respond to.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ELimitations of Breast Cancer Models\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003ECurrent advanced breast cancer models have key drawbacks. One type of model involves injecting human tumor cells into mice that lack a complete immune system, but this complicates the study of immune-targeting therapies. In a different approach, mice are manipulated at the genome level to make them cancer prone. Although their immune responses may closely resemble that of human patients, the rate of tumor development is highly variable, making these models suboptimal for scalable drug testing.\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe most common way to generate breast cancer models for immunotherapy research, however, is by injecting mouse breast cancer cells directly into healthy mice. This method is affordable and scalable, but sometimes up to 80% of mice in an experiment will not grow tumors.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETo address this, breast cancer researchers began to inject the tumor cells alongside a commercially sold gelatinous protein mixture derived from mouse cells (Matrigel), which helps tumors grow reliably. The problem with the mixture, however, is that its composition varies from batch to batch. Using the mixture therefore creates more unknown variables, affecting a mouse\u0026rsquo;s immune response in unpredictable ways.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAn unexpected solution presented itself when Thomas and O\u0026rsquo;Melia attended a regenerative medicine workshop. At the workshop, Edward Botchwey, associate professor in the \u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/\u0022\u003EWalter H. Coulter Department of Biomedical Engineering\u003C\/a\u003E, introduced a bioengineered scaffold able to modulate how immune cells filtrate into a wound site to facilitate tissue healing.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;I turned to Meghan and said, \u0026lsquo;Why don\u0026rsquo;t we see if they want to collaborate to explore if we can change how immune cells are recruited to the site where we are implanting our tumors?\u0026rsquo;\u0026rdquo; Thomas said.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThey set out to work with Botchwey and Andr\u0026eacute;s Garc\u0026iacute;a, professor of mechanical engineering and executive director of the \u003Ca href=\u0022https:\/\/research.gatech.edu\/bio\u0022\u003EParker H. Petit Institute for Bioengineering and Bioscience (IBB)\u003C\/a\u003E, to develop a scaffold to grow breast tumors.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EA Novel Scaffold to Shape the Tumor Microenvironment\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe team developed their own synthetic jelly-like matrix. They then injected triple negative breast cancer (TNBC) cells, the most aggressive type of breast cancer, alongside the matrix as a scaffold to help them grow. They found that their breast cancer tumors formed at a rate of 100% and did so faster and with lower variability in growth than when using Matrigel. Most importantly, their scaffold limited the type of immune cells that infiltrated into the tumor microenvironment. Their approach resulted in the kind of controlled environment ideal for experiments in immunotherapy drug testing.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ETaking a step further, the team created different formulations of the gel matrix by incorporating biomolecular tags readily recognized by immune cells. The tags are made of peptides and serve to recruit key immune cells to the microenvironment. Incorporating the tags enabled Thomas and O\u0026rsquo;Melia to model different subtypes of immune environments often seen in treatment-resistant TNBC.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThey then tested two of the most common types of immunotherapy drugs \u0026mdash; vaccines and immune checkpoint blockade therapy \u0026mdash; on the different subsets of cancer microenvironments.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;When we used different matrix components, we saw different effects of these drugs on the same type of cancer,\u0026rdquo; Thomas said. \u0026ldquo;There is a lot of variability related to why some patients respond to therapy or not, and until now there was no way to incorporate that into our mouse models when developing drugs.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ELooking Beyond the Lab\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe findings demonstrate the essential role a patient\u0026rsquo;s tumor immune microenvironment plays in the success of immunotherapies, stressing the importance of their new approach for future drug testing.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThomas and O\u0026rsquo;Melia\u0026rsquo;s work carries broad potential for pre-screening immunotherapy drugs for individual patients. Hypothetically, for the average cancer patient, a clinician could do a simple biopsy, determine what immune cells are present, and choose a better therapy.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThey also collaborated with Levi Wood, assistant professor of mechanical engineering, and investigators at IBB who contributed immune phenotyping for the experiments.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;Basically, by using an established technology but applied in a new way, we created a new tool to solve an old problem,\u0026rdquo; Thomas said. \u0026ldquo;The collaborative nature of this project was spectacular, and that is really intrinsic to the Georgia Tech community.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cdiv\u003E\r\n\u003Cp\u003E***\u003C\/p\u003E\r\n\u003C\/div\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022https:\/\/www.me.gatech.edu\/faculty\/thomas\u0022\u003ESusan N. Thomas\u003C\/a\u003E is an associate professor in the \u003Ca href=\u0022https:\/\/www.me.gatech.edu\/\u0022\u003EGeorge W. Woodruff School of Mechanical Engineering\u003C\/a\u003E and Woodruff Professor in the \u003Ca href=\u0022https:\/\/coe.gatech.edu\/\u0022\u003ECollege of Engineering\u003C\/a\u003E.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022https:\/\/botchweylab.gatech.edu\/\u0022\u003EEdward Botchwey\u003C\/a\u003E is an associate professor in the \u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/\u0022\u003EWalter H. Coulter Department of Biomedical Engineering\u003C\/a\u003E.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022https:\/\/www.me.gatech.edu\/faculty\/garcia\u0022\u003EAndr\u0026eacute;s J. Garc\u0026iacute;a\u003C\/a\u003E is executive director of \u003Ca href=\u0022https:\/\/research.gatech.edu\/bio\u0022\u003EIBB\u003C\/a\u003E, the Petit Director\u0026#39;s Chair in Bioengineering and Bioscience, and Regents\u0026#39; Professor in the George W. Woodruff School of Mechanical Engineering.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022https:\/\/www.me.gatech.edu\/faculty\/wood\u0022\u003ELevi Wood\u003C\/a\u003E is an assistant professor in the George W. Woodruff School of Mechanical Engineering.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: Meghan J. O\u0026#39;Melia, Adriana Mulero-Russe, Jihoon Kim, Alyssa Pybus, Deborah DeRyckere, Levi Wood, Douglas K. Graham, Edward Botchwey, Andr\u0026eacute;s J. Garc\u0026iacute;a, and Susan N. Thomas, \u0026ldquo;Synthetic matrix scaffolds engineer the in vivo tumor immune microenvironment for immunotherapy screening,\u0026rdquo; \u003Cem\u003EAdvanced Materials\u003C\/em\u003E (Jan. 6, 2022).\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EDOI\u003C\/strong\u003E: \u003Ca href=\u0022https:\/\/doi.org\/10.1002\/adma.202108084\u0022\u003Ehttps:\/\/doi.org\/10.1002\/adma.202108084\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EFUNDING\u003C\/strong\u003E: U.S. National Institutes of Health grants: R01CA207619 (SNT), U01CA214354 (SNT), R01AR062920 (AJG), R01AR062368 (AJG), S10OD016264 (AJG), T32GM008433 (MJO), and T32EB006343 (AMR)\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: Catherine Barzler\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EMedia Contact\u003C\/strong\u003E: Catherine Barzler | \u003Ca href=\u0022mailto:catherine.barzler@gatech.edu\u0022\u003Ecatherine.barzler@gatech.edu\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Using a synthetic scaffold, researchers created a novel way generate breast tumor models faster, more reliably, and with dramatically less immune variability than existing models - making them highly suitable for immunotherapy research. "}],"uid":"36123","created_gmt":"2022-03-01 21:25:02","changed_gmt":"2022-03-01 22:25:03","author":"Catherine Barzler","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2022-03-01T00:00:00-05:00","iso_date":"2022-03-01T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"655911":{"id":"655911","type":"image","title":"Susan Thomas outside hero ","body":null,"created":"1646166706","gmt_created":"2022-03-01 20:31:46","changed":"1646170580","gmt_changed":"2022-03-01 21:36:20","alt":"A headshot of Susan N. Thomas who is standing outside and smiling, wearing navy blue blazer over a white t-shirt. ","file":{"fid":"248657","name":"susan hero 2.jpg","image_path":"\/sites\/default\/files\/images\/susan%20hero%202.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/susan%20hero%202.jpg","mime":"image\/jpeg","size":340511,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/susan%20hero%202.jpg?itok=BzhWLX5v"}},"655920":{"id":"655920","type":"image","title":"Susan N. Thomas lab photo","body":null,"created":"1646167103","gmt_created":"2022-03-01 20:38:23","changed":"1646170539","gmt_changed":"2022-03-01 21:35:39","alt":"Susan N. Thomas in her lab","file":{"fid":"248660","name":"susan lab.jpg","image_path":"\/sites\/default\/files\/images\/susan%20lab.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/susan%20lab.jpg","mime":"image\/jpeg","size":393054,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/susan%20lab.jpg?itok=tdZX-GCS"}},"655921":{"id":"655921","type":"image","title":"Meghan O\u0027Melia headshot ","body":null,"created":"1646167176","gmt_created":"2022-03-01 20:39:36","changed":"1646170666","gmt_changed":"2022-03-01 21:37:46","alt":"","file":{"fid":"248667","name":"omelia headshot.png","image_path":"\/sites\/default\/files\/images\/omelia%20headshot.png","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/omelia%20headshot.png","mime":"image\/png","size":103653,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/omelia%20headshot.png?itok=PZuyp4Z4"}}},"media_ids":["655911","655920","655921"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[],"keywords":[{"id":"187915","name":"go-researchnews"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003ECatherine Barzler\u003C\/p\u003E\r\n","format":"limited_html"}],"email":["catherine.barzler@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}