NEWS OF THE WEEK
SEATTLE GENETICS HITS A KEY TARGET PHARMACEUTICALS: FDA panel gives thumbs up to antibody-drug conjugate
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N FDA ADVISORY panel has voted unanimous-
ly to recommend Seattle Genetics’ Adcetris for accelerated approval as a treatment for two types of lymphoma in patients who haven’t responded to other therapies. If the agency eventually gives the nod, Adcetris will become Seattle Genetics’ first prodAdcetris consists uct and the only approved antibody-drug conjugate of an anti-CD30 (ADC). Last summer, Pfizer withdrew Mylotarg, an ADC antibody linked for cancer, because of efficacy and safety concerns. to an antimitotic drug. ADCs have long been considered ideal cancer-fighting agents for their potential to deliver a potent cytotoxic payload by linking it to a cancer-targeting carrier. A problem, Linker Drug which plagued Mylotarg but that Seattle n Antibody Genetics seems to have overcome, is bloodstream-stable linker chemistry. After binding to a CD30-expressing cancer cell, Adcetris, or brentuximab vedotin, is taken into the cell where proteases then cleave the linker and release the cytotoxic
THE (SYNTHETIC) NOSE KNOWS BIOELECTRONICS: Chemical sensor
combines olfactory proteins and carbon nanotubes to mimic biology
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ACS N AN O
Olfactory receptors embedded in discshaped membrane mimics and attached to carbon nanotubes detect chemical vapors.
Y TETHERING mouse proteins responsible for
detecting odor molecules to carbon nanotube transistors, researchers have built a synthetic system that can “smell” chemical vapors (ACS Nano, DOI: 10.1021/nn200489j). The researchers, led by physics professor A. T. Charlie Johnson of the University of Pennsylvania, are the first “to demonstrate that reconstituted olfactory receptors can be used to recognize molecules and transduce their presence on nanotube sensors,” says Michael S. Strano, a chemical engineering professor at MIT who develops nanosensors. “What’s exciting is that these receptors are membrane proteins and typically very difficult to place correctly at a sensor interface.” Johnson and coworkers embedded the olfactory receptors in mimics of WWW.CEN-ONLINE.ORG
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agent monomethyl auristatin E. This approach spares healthy cells and reduces toxic side effects. The panel was impressed with signs from small-scale trials that Adcetris is effective, according to investment analysts who followed the proceedings. Although the advisory panel’s vote isn’t binding, FDA often follows such advice; the agency is expected to make a decision by Aug. 30. Seattle Genetics had hoped for a full approval of the new ADC. The accelerated approval recommended by the panel requires less clinical data up front but is conditioned on postapproval efficacy and safety studies. FDA doesn’t consider the company’s ongoing Phase III trial as meeting this condition, the analysts report, and it has warned Seattle Genetics to work fast to design a new trial to avoid delays. In the company’s favor, however, is that new trials can likely also be used to expand testing against similar cancers. “We would assume that at this point Seattle Genetics will do everything to come to agreement with the FDA to ensure approval,” Leerink Swann stock analysts wrote in a report to clients. Sales of Adcetris are expected to exceed $100 million in its first full year on the market. Seattle Genetics is developing the drug with Millennium, part of Japan’s Takeda Pharmaceutical. In June, European regulators accepted a filing from Takeda, which has marketing rights outside the U.S. and Canada.—ANN THAYER
cell membranes before attaching them to the nanotubes. They exposed the devices to vapor streams containing different odorant molecules and measured the current through the nanotube transistor. The signal disappeared when the odorants were removed. Johnson and coworkers used two types of membrane mimics, the surfactant digitonin and lipidprotein particles known as nanodiscs. Both systems responded comparably to vapors, but the nanodiscs extended the sensors’ shelf life. The digitonin sensors worked for about five days, but the nanodisc devices remained stable for more than two months. Because membrane proteins are difficult to express and purify, Johnson and his team used only three mouse olfactory receptors. “If you want something like a nose in biology, you need a couple hundred different olfactory receptor proteins,” Johnson says. Olfactory receptors are a subset of a larger class of membrane proteins known as G-protein-coupled receptors (GPCRs). Johnson would like to develop sensors that can convert the binding of other GPCRs, many of which are drug targets, into signals. “I suspect the method would be generic to this entire receptor class,” says David R. Walt, a chemistry professor at Tufts University who also develops chemical sensors. Still, he says, “there remains a lot of work to be done before one can expect such systems to be stable for longer periods of time and to achieve the sensitivity of the mammalian nose.”—CELIA ARNAUD
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