{"id":2680,"date":"2018-11-01T10:01:53","date_gmt":"2018-11-01T17:01:53","guid":{"rendered":"https:\/\/keck.usc.edu\/news\/building-a-better-car\/"},"modified":"2023-11-26T08:27:15","modified_gmt":"2023-11-26T16:27:15","slug":"building-a-better-car","status":"publish","type":"post","link":"https:\/\/keck.usc.edu\/news\/building-a-better-car\/","title":{"rendered":"Building A Better \u201cCAR\u201d"},"content":{"rendered":"\n \n \n\n\n\n\n\n\n\n
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\n\n \n Press Release<\/span>\n\n\n\n<\/div>\n \n \n
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Building A Better \u201cCAR\u201d<\/h1>\n\n\n<\/div>\n \n \n
\n \n November 01, 2018<\/span>\n <\/div>\n \n \n
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Professors Stacey Finley, Nick Graham and Pin Wang\u00a0(Image\/Created by Michelle Henry)<\/figcaption>\n <\/figure>\n \n \n \n\n<\/div>\n \n\n <\/div><\/div>\n\r\n\r\n\n\n \n \n\n\n\n\n\n\n\n
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In his 1971 State of the Union address, President Richard Nixon dedicated the country to finding a cure for cancer. \u201cThe time has come in America when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dreaded disease,\u201d he said. \u201cLet us make a total national commitment to achieve this goal.\u201d<\/p>\n

In the nearly five decades since, real progress has been made in the war against cancer but not enough. Cancer remains the second-leading cause of death in the United States. This year, an estimated 1.7 million new cases will be diagnosed, with nearly 610,000 people expected to die from the disease, according to the\u00a0National Cancer Institute<\/a>.<\/p>\n

Fortunately, several recent cancer treatments show considerable promise. Among them is\u00a0Chimeric Antigen Receptor (CAR) T cell therapy<\/a>, which the\u00a0American Society of Clinical Oncology<\/a>\u00a0recently named the \u201c2018 Advance of the Year.\u201d Three USC Viterbi researchers \u2013\u00a0Assistant Professor Stacey Finley<\/a>,\u00a0Professor Pin Wang<\/a>\u00a0and\u00a0Assistant Professor Nick Graham<\/a>\u00a0\u2013 have just published a paper in \u201cBiophysical Journal<\/a>\u201d that sheds light on how this new treatment works, information that could one day result in better cancer therapies with fewer side effects.<\/p>\n

\u201cWe\u2019re trying to dig into the molecular mechanisms,\u201d said Graham, an assistant professor of chemical engineering and materials science. \u201cBy understanding how the CAR T cells work, we could try to design better ones.\u201d<\/p>\n

When the immune system functions normally, immune cells move around the body and look for pathogens that don\u2019t belong and kill them. However, cancer cells can mask themselves, making it harder for the good cells, such as T cells, to kill them.<\/p>\n

With CAR T cell therapy, a person\u2019s T cells are removed,\u00a0 genetically engineered with proteins, and then injected back into the patient. The resulting CAR T cells are much better at fighting cancer cells. That\u2019s because these modified CAR T cells have an engineered protein receptor, the CAR, that can bind to cancer cells. When this occurs, a signal from the CAR tells the T cell to begin destroying the cancer by secreting the chemicals perforin and granzyme.<\/p>\n

CAR T cell therapies<\/strong><\/p>\n

Earlier this year, the U.S. Food and Drug Administration approved the first CAR T cell therapy for the treatment of some people with advanced leukemia and a form of lymphoma, both blood cancers. Early results have shown great promise. However, in early tests, the CAR-T cell therapies have so far proven much less effective against breast, lung, prostate and other solid-tumor cancers. Additionally, some people undergoing CAR T cell therapy have experienced significant side effects; a few have even died.<\/p>\n

\"\"
Professors Stacey Finley, Nick Graham and Pin Wang\u00a0(Image\/Created by Michelle Henry)<\/figcaption><\/figure>\n

The trio of USC researchers hope their work will greatly improve CAR T cell therapies by uncovering the complicated process by which CARs activate cancer fighting cells. Specifically, they are examining a process called phosphorylation, which is a chemical reaction that occurs when the CAR receptor bumps up against a cancer cell and sends a signal to the T cell to attack the bad cells.<\/p>\n

\u201cI think what\u2019s most exciting is that we\u2019re really adding to the field an understanding of which sites on the CAR are becoming phosphorylated, how quickly that happens and the amount of phosphorylation of each site,\u201d said Finley,\u00a0 the Gordon S. Marshall Early Career Chair and assistant professor of biomedical engineering, chemical engineering and materials science and biological sciences.<\/p>\n

Through their research, Finley, Wang and Graham have learned when and how much\u00a0phosphorylation<\/a>\u00a0occurs on the CAR\u2019s six sites, which, in an imperfect analogy, could be imagined as \u201cdocking hubs,\u201d in Graham\u2019s words. Additionally, they have found that no \u201cgatekeeper\u201d exists, meaning that no single CAR site must be phosphorylated before the others. Until now, scholars only had a general idea about the phosphorylation process, making it difficult to bioengineer CAR T cells that could successfully fight against complex and complicated breast, lung and other solid-tumor cancers.<\/p>\n

Better cancer-fighting CARs<\/strong><\/p>\n

Going forward, Finley, Wang and Graham hope to leverage their findings into engineering more effective cancer-fighting CARs with fewer side effects. This could mean having phosphorylation take place quicker and more intensely at certain CAR sites, depending on the complexity of the targeted cancer cells. Alternately, the USC researchers might engineer CARs to phosphorylate less, thereby preventing the cancer-fighting T- and other cells from becoming too aggressive and killing healthy cells \u2013 a problem that has cropped up with early CAR T cell cancer treatments.<\/p>\n

Already, Finley has built quantitative models that holds great promise.<\/p>\n

\u201cOnce we have these tools and quantitative models, we should be able to apply them to a variety of different designs of CARs,\u201d \u00a0said Finley, whose research group has an expertise in mathematical models. \u201cMaybe you could use a model, before you do an experiment, to see if this new design would work. Instead of having to do as many tedious experiments in the lab, you could build a predictive mathematical model to screen the best design.\u201d<\/p>\n

Added Wang, the Zohrab A. Kaprielian Fellow in Engineering and professor of chemical engineering and materials science, and biomedical engineering: \u201cIf you want to make the T cells more potent, the question is how best to design the CAR. That\u2019s our research\u2019s goal, I think.\u201d<\/p>\n

By\u00a0Marc Ballon<\/a><\/strong><\/p>\n\n\n\n<\/div>\n <\/div>\n\n\n <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":168,"featured_media":2682,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[6],"tags":[139,135],"class_list":["post-2680","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-press-release","tag-medicine-engineering-science-and-humanities-program","tag-mesh"],"acf":[],"yoast_head":"\nBuilding A Better \u201cCAR\u201d<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/keck.usc.edu\/news\/building-a-better-car\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" 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