First (and massive) whole-genome study of IBD in African Americans

In African Americans, the genetic risk landscape for inflammatory bowel disease (IBD) is very different from that of people with European ancestry, according to results of the first whole-genome study of IBD in African Americans. The authors say that future clinical research on IBD needs to take ancestry into account. Findings of the multi-center study, which analyzed the whole genomes of more than 1,700 affected individuals with Crohn’s disease and ulcerative colitis and more than Read more

Emory researchers SNARE new Alzheimer’s targets

Diving deep into Alzheimer’s data sets, a recent Emory Brain Health Center paper in Nature Genetics spots several new potential therapeutic targets, only one of which had been previous linked to Alzheimer’s. The Emory analysis was highlighted by the Alzheimer’s site Alzforum, gathering several positive comments from other researchers. Thomas Wingo, MD Lead author Thomas Wingo and his team -- wife Aliza Wingo is first author – identified the targets by taking a new approach: tracing Read more

oncolytic viruses

Engineered “stealth bomber” virus could be new weapon against metastatic cancer

Many cancer researchers can claim to have devised “smart bombs.” What has been missing is the stealth bomber – a delivery system that can slip through the body’s radar defenses. 

Oncolytic viruses, or viruses that preferentially kill cancer cells, have been discussed and tested for decades. An oncolytic virus against melanoma was approved by the FDA in 2015. But against metastatic cancers, they’ve always faced an overwhelming barrier: the human immune system, which quickly captures viruses injected into the blood and sends them to the liver, the body’s garbage disposal.

Researchers at Emory and Case Western Reserve have now circumvented that barrier. They’ve re-engineered human adenovirus, so that the virus is not easily caught by parts of the innate immune system.

The re-engineering makes it possible to inject the virus into the blood, without arousing a massive inflammatory reaction.

A cryo-electron microscopy structure of the virus and its ability to eliminate disseminated tumors in mice were reported on November 25 in Science Translational Medicine.

“The innate immune system is quite efficient at sending viruses to the liver when they are delivered intravenously,” says lead author Dmitry Shayakhmetov, PhD. “For this reason, most oncolytic viruses are delivered directly into the tumor, without affecting metastases. In contrast, we think it will be possible to deliver our modified virus systemically at doses high enough to suppress tumor growth — without triggering life-threatening systemic toxicities.”

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

To fight cancer, mix harmless reovirus with ‘red devil’

A recent paper in Journal of Virology mixes tried-and-true cancer-fighting tactics with the exotic. Sort of a peanut-butter-and-chocolate story, but definitely not tasty!

The tried and true is doxorubicin (Adriamycin), the notorious ‘red devil’ chemotherapy drug, which has been around for decades. On the exotic side, we have oncolytic viruses – viruses retuned to attack cancer cells more than healthy cells. This idea finally made it to FDA approval in 2015 in the form of a re-engineered herpes virus directed against melanoma.

Bernardo Mainou’s lab in the Department of Pediatrics is combining both of these approaches together. He and his team are looking to supercharge reoviruses, a mostly harmless type of virus that has been adapted into an anticancer agent. A Canadian company has brought its reovirus forward into several cancer clinical trials, but its product has not gotten to the finish line.

In the JVI paper, graduate students Roxana Rodriguez-Stewart, Jameson Berry and their colleagues infected triple-negative breast cancer cells with a variety of reoviruses, in an effort to select for those that replicate better in those cells. They also looked for drugs that enhance viral infection of those cells, and landed on doxorubicin and related drugs. Doxorubicin is part of a class of anticancer drugs that inhibit topoisomerases, enzymes that unwind DNA as part of the process of replication.

Yesterday at the GDBBS graduate research symposium, Berry gave a talk about the next step: attaching the souped-up reovirus to doxorubicin.

Three varieties of reovirus were grown together in breast cancer cells to select for efficient replication. 

 

 

 

 

Posted on by Quinn Eastman in Cancer Leave a comment

Explainer: oncolytic viruses

A recent publication from Bill Kaiser’s and Ed Mocarski’s labs in Cell Host & Microbe touches on a concept that needs explaining: oncolytic viruses.

Viruses have been subverting the machinery of healthy cells for millions of years, and many viruses tend to infect particular tissues or cell types. So they are a natural starting point for researchers to engineer oncolytic viruses, which preferentially infect and kill cancer cells.

Several oncolytic viruses have progressed to advanced clinical trials. Amgen’s “T-Vec”, a modified herpes simplex virus, could be the first to be approved by the FDA this year based on its efficacy against metastatic melanoma.  Read more

Posted on by Quinn Eastman in Cancer Leave a comment