Genetic Engineering & Biotechnology News

JUL 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Instead, as a newly released best-selling book suggests, the Theranos story is a cautionary tale. The book, Bad Blood: Secrets and Lies in a Silicon Valley Startup, is by investigative reporter John Carreyrou, who broke the Theranos story for the Wall Street Journal back in 2015. Besides detailing the questionable goings-on at Theranos, Bad Blood warns that Silicon Valley–style hype—which is hardly unique to Theranos—can result in harm beyond the rhetorical. It can waste enormous amounts of time and money. Even worse, it can take a sinister turn and threaten people's lives—especially if it see page 22 Kathy Liszewski Tumorigenesis is to healthy tissue what xenoforming, or hostile terraforming, is to the planet. Both tumorigenesis and xenoforming are processes that alter the environment so that it may become less hospi- table to its usual inhabitants, and more welcoming to that which is alien. But while xenoforming is just science fiction—the inspiration for "alien kudzu," "meat moss," and other horrors—tumorigenesis is all too real. In tumorigenesis, the world that is warred over is the tumor microenvironment (TME), which consists of non- malignant cells and extracellular matrix elements that are curiously accommodating toward malignant cells. The TME becomes more alien, more a travesty of healthy tis- sue, as tumorigenesis proceeds, perverting cellular com- munications and suppressing immune defenses. If tumorigenesis is to be slowed or reversed, the TME must be reclaimed and restored, piecemeal if need be, molecule by molecule, pathway by pathway, and cell by cell. TME components of the highest importance include immunoregulatory elements. If such elements could be manipulated rightly—if they could be sub- jected to "immunoforming"—they would rouse rather than suppress immune defenses. Immunoforming was a key theme at "Targeting the Tumor Microenvironment," a recent Cambridge Health- tech Institute conference. At this event, scientists shared the latest advances in understanding and manipulating the TME. For example, conference speakers and attend- ees discussed strategies for targeting TME components and reversing Reclaim the Tumor Microenvironment via "Immunoforming" Bad Blood Has the Goods on Theranos Christina Bennett The rise and fall of Theranos, the blood-testing company founded and led by Stanford University dropout Elizabeth Holmes, doesn't qualify as tragedy, for tragedy requires the ruin of a noble character. See caption below left. Scientists at Vaccinex are targeting Semaphorin 4D (SEMA4D), a cell-signaling protein that is highly expressed on tumor margins (see figure top right). It acts to restrict the movement of tumoricidal immune cells into the tumor microenvironment (TME). Antibody blockade of SEMA4D facilitates migration of antigen-presenting cells (APCs) and T cells into the tumor. (A) SEMA4D expression at the invasive margin of murine colon26 tumors restricts infiltration of CD11c + dendritic cells, expressing its cognate receptor, into the TME. Anti-SEMA4D monoclonal antibody (mAb) promotes infiltration of proinflammatory CD11c + / F4-80 + APCs. (B) Proinflammatory APCs recruit and activate cytotoxic CD8 + T cells within the TME. (C) Colon26 tumor– bearing mice were treated with control immunoglobulin or anti-SEMA4D/mAb67 antibodies for four weeks. Tumors were harvested, and formalin-fixed paraffin-embedded tissue sections were stained by immunohistochemistry. Courtesy of Alfred A. Knopf July 2018 see page 14 See Story on p26. The Scoop Tracking MicroRNAs to Study Brain Dysfunction 6 CAR T-Cell Therapies with a Bispecific Twist 24 Cell Line Validation in Biomanufacturing 16 CAR T Cells Show Solid Progress 26

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