Featured Research

from universities, journals, and other organizations

Injected bacteria shrink tumors in rats, dogs and humans

Date:
August 13, 2014
Source:
Johns Hopkins Medicine
Summary:
A modified version of the Clostridium novyi (C. novyi-NT) bacterium can produce a strong and precisely targeted anti-tumor response in rats, dogs and now humans, according to a new report. In its natural form, C. novyi is found in the soil and, in certain cases, can cause tissue-damaging infection in cattle, sheep and humans. The microbe thrives only in oxygen-poor environments, which makes it a targeted means of destroying oxygen-starved cells in tumors that are difficult to treat with chemotherapy and radiation.

This is a hematoxylin and eosin stain of a C. novyi-NT treated dog tumor. Lighter pink areas areas denote tumor necrosis next to areas with viable tumor cells. Black patches are calcified areas of tissue.
Credit: David L. Huso and Baktiar Karim of the Johns Hopkins Department of Pathology.

A modified version of the Clostridium novyi (C. novyi-NT) bacterium can produce a strong and precisely targeted anti-tumor response in rats, dogs and now humans, according to a new report from Johns Hopkins Kimmel Cancer Center researchers.

Related Articles


In its natural form, C. novyi is found in the soil and, in certain cases, can cause tissue-damaging infection in cattle, sheep and humans. The microbe thrives only in oxygen-poor environments, which makes it a targeted means of destroying oxygen-starved cells in tumors that are difficult to treat with chemotherapy and radiation. The Johns Hopkins team removed one of the bacteria's toxin-producing genes to make it safer for therapeutic use.

For the study, the researchers tested direct-tumor injection of the C. novyi-NT spores in 16 pet dogs that were being treated for naturally occurring tumors. Six of the dogs had an anti-tumor response 21 days after their first treatment. Three of the six showed complete eradication of their tumors, and the length of the longest diameter of the tumor shrunk by at least 30 percent in the three other dogs.

Most of the dogs experienced side effects typical of a bacterial infection, such as fever and tumor abscesses and inflammation, according to a report on the work published online Aug. 13 in Science Translational Medicine.

In a Phase I clinical trial of C. novyi-NT spores conducted 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. "She had a very vigorous inflammatory response and abscess formation," according to Nicholas Roberts, Vet.M.B., Ph.D. "But at the moment, we haven't treated enough people to be sure if the spectrum of responses that we see in dogs will truly recapitulate what we see in people."

"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, " said Shibin Zhou, M.D., Ph.D., associate professor of oncology at the Cancer Center. Zhou is also the director of experimental therapeutics at the Kimmel Cancer Center's Ludwig Center for Cancer Genetics and Therapeutics. He and colleagues at Johns Hopkins 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, which grew out of the observation that some cancer patients who contracted serious bacterial infections showed cancer remission.

The researchers focused on soft tissue tumors because "these tumors are often locally advanced, and they have spread into normal tissue," said Roberts, a Ludwig Center and Department of Pathology researcher. The bacteria cannot germinate in normal tissues and will only attack the oxygen-starved or hypoxic cells in the tumor and spare healthy tissue around the cancer.

Verena Staedtke, M.D., Ph.D., 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 the C. noyvi-NT spore injection.

The researchers then extended their tests of the injection to dogs. "One of the reasons that we treated dogs with C. novyi-NT before people is because dogs can be a good guide to what may happen in people," Roberts said. The dog tumors share many genetic similarities with human tumors, he explained, and their tumors appeared spontaneously as they would in humans. Dogs are also treated with many of the same cancer drugs as humans and respond similarly.

The dogs showed a variety of anti-tumor responses and inflammatory side effects.

Zhou said that study of the C. novyi-NT spore injection in humans is ongoing, but the final results of their treatment are not yet available. "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."

It may be possible to combine traditional treatments like chemotherapy with the C. novyi-NT therapy, said Zhou, who added that the researchers have already studied these combinations in mice.

"Some of these traditional therapies are able to increase the hypoxic region in a tumor and would make the bacterial infection more potent and increase its anti-tumor efficiency," Staedtke suggested. "C. novyi-NT is an agent that could be combined with a multitude of chemotherapy agents or radiation."

"Another good thing about using bacteria as a therapeutic agent is that once they're infecting the tumor, they can induce a strong immune response against tumor cells themselves," Zhou said.

Previous studies in mice, he noted, suggest that C. novyi-NT 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.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. N. J. Roberts, L. Zhang, F. Janku, A. Collins, R.-Y. Bai, V. Staedtke, A. W. Rusk, D. Tung, M. Miller, J. Roix, K. V. Khanna, R. Murthy, R. S. Benjamin, T. Helgason, A. D. Szvalb, J. E. Bird, S. Roy-Chowdhuri, H. H. Zhang, Y. Qiao, B. Karim, J. McDaniel, A. Elpiner, A. Sahora, J. Lachowicz, B. Phillips, A. Turner, M. K. Klein, G. Post, L. A. Diaz, G. J. Riggins, N. Papadopoulos, K. W. Kinzler, B. Vogelstein, C. Bettegowda, D. L. Huso, M. Varterasian, S. Saha, S. Zhou. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Science Translational Medicine, 2014; 6 (249): 249ra111 DOI: 10.1126/scitranslmed.3008982

Cite This Page:

Johns Hopkins Medicine. "Injected bacteria shrink tumors in rats, dogs and humans." ScienceDaily. ScienceDaily, 13 August 2014. <www.sciencedaily.com/releases/2014/08/140813173906.htm>.
Johns Hopkins Medicine. (2014, August 13). Injected bacteria shrink tumors in rats, dogs and humans. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2014/08/140813173906.htm
Johns Hopkins Medicine. "Injected bacteria shrink tumors in rats, dogs and humans." ScienceDaily. www.sciencedaily.com/releases/2014/08/140813173906.htm (accessed October 30, 2014).

Share This



More Health & Medicine News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Fauci Says Ebola Risk in US "essentially Zero"

Fauci Says Ebola Risk in US "essentially Zero"

AP (Oct. 30, 2014) NIAID Director Anthony Fauci said the risk of Ebola becoming an epidemic in the U.S. is essentially zero Thursday at the Washington Ideas Forum. He also said an Ebola vaccine will be tested in West Africa in the next few months. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Nurse Defies Ebola Quarantine With Bike Ride

Nurse Defies Ebola Quarantine With Bike Ride

AP (Oct. 30, 2014) A nurse who vowed to defy Maine's voluntary quarantine for health care workers who treated Ebola patients followed through on her promise Thursday, leaving her home for an hour-long bike ride. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Microsoft Launches Fitness Band After Accidental Reveal

Microsoft Launches Fitness Band After Accidental Reveal

Newsy (Oct. 30, 2014) Microsoft accidentally revealed its upcoming fitness band on Wednesday, so the company went ahead and announced it. Video provided by Newsy
Powered by NewsLook.com
Bracing to Meet a Killer: Aid Workers Prep for Ebola in Geneva

Bracing to Meet a Killer: Aid Workers Prep for Ebola in Geneva

AFP (Oct. 30, 2014) At the International Federation of Red Cross and Red Crescent Societies, around 30 doctors, nurses, lab technicians and water and sanitation workers are gathered for a crash-course in how to safely deal Ebola. Duration: 01:31 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins