Mutations as munitions: Neoantigen vaccines get a closer look as cancer treatment

nm0216-122-i1In 2010, the Dendreon company received the news it had been hoping for: the US Food and Drug Administration had approved its therapeutic cancer vaccine Provenge for prostate cancer. At the time of Provenge’s approval, the headlines hailed it as groundbreaking, and they noted a surge in the price of Dendreon’s stock as the company announced its $93,000 price tag for the therapy. But enthusiasm fizzled when the company later revealed that fewer people used the therapy than expected, and in November 2014 the company filed for bankruptcy. Continue reading “Mutations as munitions: Neoantigen vaccines get a closer look as cancer treatment”

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Setback prompts rethink of latency-reversing strategy to eliminate HIV infection

Antiretroviral drugs have been spectacularly effective in controlling HIV by hobbling the virus’s ability to infect cells, but they do not deplete the reservoirs of latently infected cells that remain a major barrier to a cure. One appealing solution to this problem has been latency-reversing agents (LRAs) that can reactivate the dormant virus, bringing it out of hiding so that it can be targeted and killed. The first-generation LRAs, however, have recently hit a snag. Four frontrunners that had shown potential in cell-culture models and preliminary clinical studies are
only minimally effective in a patient cell assay, shows a new study. A fifth compound, although more potent, is likely to be too toxic for
clinical use.

[Read more at Nature Reviews Drug Discovery (paywall) or download PDF // May 30, 2014]

The Modelling Challenge

Schizophrenia FeatureWhen Patricio O’Donnell started his lab in 1997 at Albany Medical College in New York, schizophrenia research seemed to be moving forward after a long period of stagnation.

For several decades, attention had focused on the idea that the disease was caused by elevated dopamine levels in the brain, particularly in the striatum, a nugget of brain tissue nestled under the cortex. But by the 1990s, the dopamine hypothesis was proving inadequate to fully explain the disease. In vivo imaging with computed tomography and magnetic resonance imaging, and data from post-mortem studies in people with schizophrenia, pointed to cortical effects and implicated other neurotransmitter systems, such as glutamate and serotonin. Biologists were also learning to create transgenic mouse models of the disease, providing a set of tools with which to investigate genetic and aetiological factors.

[Read more at Nature Outlook (paywall) or download PDF // April 3, 2014]

Industrial Immunology

Olivia Schneider realized early in her graduate work on immune-cell signalling that she had no interest in becoming an academic researcher. “I didn’t want to work in a lab, or to write grants,” she says. In 2009, when she finished her PhD at the University of Cincinnati in Ohio, the global recession was in full swing and employment options looked scarce. Her husband had a well-paid job in the area, so relocating was impractical. Then Schneider saw an advert for part-time work through a local contract-research organization, doing tissue culture and cloning for a recombinant-protein manufacturer called Shenandoah Biotechnology in Warwick, Pennsylvania. “I just wanted to get my foot into biotech in some regard,” she says. “I took this position — that I was way overqualified for — with the hope that it would turn into something else.”

[Read more at Nature Jobs // August 14, 2013]

Heavy drugs draw heavy interest from pharma backers

It’s an age-old problem in drug development: a compound that seems to exert its desired effects against cells in a Petri dish, but flops in vivo, either in animal models or, later, in humans. One common reason for such failures is how the body metabolizes drugs. Enzymes in the liver can break down molecules quickly, substantially limiting their potency. They might produce toxic metabolites in the process to boot.

If you could fortify the chemical bonds that hold those drugs together, thereby modulating the metabolism of the compound, would they be more efficacious?  A trio of biotech companies has been banking on this prospect for the last decade, and their efforts are starting to trickle into the clinic.

[Read more at Nature Medicine (paywall) or download PDF // June 6, 2013]

Momentum grows to make ‘personalized’ medicine more ‘precise’

In 2009, Wisconsin clinicians sequenced all the protein-coding DNA of a very ill 4-year-old boy named Nicholas Volker. They used the results to pinpoint a gene mutation at the root of his life-threatening gut inflammation, as well as to identify a risky but ultimately effective treatment. Nicholas’s story was hailed as one of the first successes in the long-promised goal of using sequencing to steer clinical decisions. But as the approach proliferates in the treatment of rare genetic diseases, cancers and other areas of medicine, researchers say it’s time to change both the name and the framework of a field that for more than a decade has been termed ‘personalized medicine’.

[Read more at Nature Medicine (paywall) or download PDF // March 6, 2013]

A smorgasboard of opportunity

Tara McHughTara McHugh recalls the JustFruit bar with more than a dollop of pride. In her early days at the US Department of Agriculture (USDA), McHugh led development of the technology for making 100% fruit bars, and then helped apple and pear growers to launch a company, Gorge Delights, to manufacture them. “We wanted to get people to eat more fruit,” she says. The firm, based in North Bonneville, Washington, still sells the product a decade later, and even now it occasionally checks in with manufacturing questions, says McHugh, leader of processed-foods research at the USDA’s site in Albany, California.

[Read more at Naturejobs // October 31, 2012]

Can a Pill Treat Autism?

Until now, attempts at treating autism have been limited to drugs that target peripheral symptoms such as anxiety, aggression and repetitive behaviors. But researchers hope that data from a crop of new drugs in development will allow them, for the first time, to treat an underlying mechanism of the condition, potentially helping those with autism to communicate.

[Read more at Scientific American // October 16, 2012]