JIJITANG2014-11-22 12:44 AM

TOXIC BACTERIA SAFELY SHRINK CANCER




A bacterium that is naturally toxic to cattle, sheep, and humans can be tweaked to fight difficult-to-treat cancer tumors .


The modified version of Clostridium novyi bacterium produced strong and precisely targeted results in cancers in rats , dogs , and now a human subject, scientists report.


Before injecting spores into tumors in test subjects, researchers removed one of the bacterium’s toxin-producing genes to make it safer for therapeutic use, though it still caused side effects .


“ One advantage of using bacteria to treat cancer is that you can modify these bacteria relatively easily , to equip them with other therapeutic agents , or make them less toxic as we have done here , ” says Shibin Zhou , associate professor of oncology at Johns Hopkins Kimmel Cancer Center .


In its natural form , C. novyi is found in the soil and can contaminate open wounds and cause tissue-damaging and potentially fatal infection in grazing animals and humans .


The microbe thrives only in oxygen-poor environments . That makes it suitable for destroying oxygen-starved cells in tumors that are difficult to treat with chemotherapy and radiation; at the same time ,  it spares nearby healthy , oxygen-rich tissue .


EARLY IMMUNOTHERAPY


For a new study published in Science Translational Medicine , researchers tested direct-tumor injection of modified C. novyi spores in 16 pet dogs being treated for naturally occurring tumors. Within 21 days , tumors were eradicated in three dogs and shrunk by at least 30 percent in three others .


Most of the dogs experienced side effects typical of a bacterial infection, such as fever and tumor abscesses and inflammation .


In a Phase I clinical trial at MD Anderson Cancer Center , a patient with an advanced soft tissue tumor in the abdomen received the spore injection directly into a metastatic tumor in her arm . The treatment significantly reduced the tumor in and around the bone, but with side effects similar to those the dogs experienced .


Zhou and colleagues began exploring C. novyi’s cancer-fighting potential more than a decade ago after studying hundred-year-old accounts of an early immunotherapy called Coley toxins . That treatment evolved from the observation that some cancer patients with serious bacterial infections showed cancer remission .


Verena Staedtke , a Johns Hopkins neuro-oncology fellow, first tested the spore injection in rats with implanted brain tumors called gliomas . Microscopic evaluation of the tumors showed that the treatment killed tumor cells but spared healthy cells just a few micrometers away .


The treatment also prolonged the rats’ survival , with treated rats surviving an average of 33 days after the tumor was implanted , compared with an average of 18 days in rats that did not receive spore injection .


The researchers extended their tests to dogs because their cancer has many genetic similarities with human tumors . Dogs are also treated with many of the same cancer drugs as humans and respond similarly .


COMBINED TREATMENTS


Study of the spore injection in humans is ongoing, and final results are not yet available , Zhou says .


“ We expect that some patients will have a stronger response than others, but that’s true of other therapies as well . Now , we want to know how well the patients can tolerate this kind of therapy ,” he says .


It may be possible to combine traditional treatments like chemotherapy with the modified C. novyi therapy , Zhou says . He and colleagues have already studied these combinations in mice .


Previous studies in mice suggest that modified C. novyi may help create a lingering immune response that fights metastatic tumors long after the initial bacterial treatment , but this effect remains to be seen in the dog and human studies .


Researchers from Johns Hopkins , BioMed Valley Discoveries Inc., MD Anderson Cancer Center ; Animal Clinical Investigation LLC , the Veterinary Cancer Center , VCA Great Lakes Veterinary Specialists , Friendship Hospital for Animals , BluePearl Veterinary Partners , Veterinary Specialty Hospital of San Diego , City of Angels Veterinary Specialty Center and Southern Arizona Veterinary Specialty and Emergency Center contributed to the study .


BioMed Valley Discoveries , the Virginia and D.K. Ludwig Fund for Cancer Research, the Maryland Cigarette Restitution Fund , the Commonwealth Fund, Swim Across America , the Burroughs Wellcome Career Award for Medical Scientists , Voices Against Brain Cancer , the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Clinician Scientist Award , the National Cancer Institute , and the National Institute of Neurological Diseases and Stroke funded the research .



Original Article:

《Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses》, Published on Journal《The Science》 in August , 2014 .


http://www.jijitang.com/article/546ef91063c5da8d682ebda6

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