Featured Research

from universities, journals, and other organizations

Trojan Horse For Ovarian Cancer: Nanoparticles Turn Immune System Soldiers Against Tumor Cells

Date:
July 16, 2009
Source:
Dartmouth-Hitchcock Medical Center
Summary:
Immunologists have devised a Trojan horse to help overcome ovarian cancer, unleashing a surprise killer in the surroundings of a hard-to-treat tumor.

In a feat of trickery, Dartmouth Medical School immunologists have devised a Trojan horse to help overcome ovarian cancer, unleashing a surprise killer in the surroundings of a hard-to-treat tumor.

Related Articles


Using nanoparticles--ultra small bits-- the team has reprogrammed a protective cell that ovarian cancers have corrupted to feed their growth, turning the cells back from tumor friend to foe. Their research, published online July 13 for the August Journal of Clinical Investigation, offers a promising approach to orchestrate an attack against a cancer whose survival rates have barely budged over the last three decades.

"We have modulated elements of the tumor microenvironment that are not cancer cells, reversing their role as accomplices in tumor growth to attackers that boost responses against the tumor," said Dr. Jose Conejo-Garcia, assistant professor of microbiology and immunology and of medicine, and a researcher at Dartmouth-Hitchcock's Norris Cotton Cancer Center, who led the research. "The cooperating cells hit by the particles return to fighters that immediately kill tumor cells."

The study, in mice with established ovarian tumors, involves a polymer now in clinical trials for other tumors. The polymer interacts with a receptor that senses danger to activate cells that trigger an inflammatory immune response.

The Dartmouth work focuses on dendritic cells--an immune cell particularly abundant in the ovarian cancer environment. It does take direct aim at tumor cells, so it could be an amenable adjunct to other current therapies.

"That's the beautiful part of story--people usually inject these nanoparticles to target tumor cells. But we found that these dendritic cells that are commonly present in ovarian cancer were preferentially and avidly engulfing the nanoparticles. We couldn't find any tumor cells taking up the nanoparticles, only the dendritic cells residing in the tumor," explained Juan R. Cubillos-Ruiz, graduate student and first author.

Dendritic cells are phagocytes--the soldiers of the immune system that gobble up bacteria and other pathogens, but ovarian cancer has co-opted them for its own use, he continued. "So we were trying to restore the attributes of these dendritic cells--the good guys; they become Trojan horses."

Cancer is more than tumor cells; many other circulating cells including the dendritic phagocytes converge to occupy nearby space. The dendritic cells around ovarian cancer scoop up the nanocomplexes, composed of a polymer and small interfering RNA (siRNA) molecules to silence their immunosuppressive activity.

Nanoparticle incorporation transforms them from an immunosuppressive to an immunostimulatory cell type at tumor locations, provoking anti-tumor responses and also directly killing tumor cells. The effect is particularly striking with an siRNA designed to silence the gene responsible for making an immune protein called PD-L.

The new findings also raise a warning flag about the use of gene silencing complexes in cancer treatment. Inflammation is a helpful immune response, but the researchers urge caution when using compounds that can enhance inflammation in a patient already weakened by cancer.

Ovarian cancer, which claims an estimated 15,000 US lives a year, is an accessible disease for nanoparticle delivery, according to the investigators. Instead of systemic administration, complexes can be put directly into the peritoneal cavity where the phagocytes take them up.

Samples of human ovarian cancer cells show similar responses to nanoparticle stimulation, the researchers observed, suggesting feasibility in the clinical setting. It could be part of a "multimodal approach," against ovarian cancer, said Conejo-Garcia also a member of the Dartmouth's Norris Cotton Cancer Center. "The prevailing treatment is surgical debulking, followed by chemotherapy. Our findings could complement those because they target not the tumor cells themselves, but different cells present around the tumor."

Co-authors are Xavier Engle, Uciane K. Scarlett, Diana Martinez, Amorette Barber, Raul Elgueta, Li Wang, Yolanda Nesbeth and Charles Sentman of Dartmouth; Yvon Durant of University of New Hampshire, Andrew T Gewirtz of Emory, and Ross Kedl of University of Colorado.

The work was supported by grants from the National Institutes of Health, including the National Cancer Institute and National Center for Research Resources, a Liz Tilberis Award from the Ovarian Cancer Research Fund, and the Norris Cotton Cancer Center Nanotechnology Group Award.


Story Source:

The above story is based on materials provided by Dartmouth-Hitchcock Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Dartmouth-Hitchcock Medical Center. "Trojan Horse For Ovarian Cancer: Nanoparticles Turn Immune System Soldiers Against Tumor Cells." ScienceDaily. ScienceDaily, 16 July 2009. <www.sciencedaily.com/releases/2009/07/090715160821.htm>.
Dartmouth-Hitchcock Medical Center. (2009, July 16). Trojan Horse For Ovarian Cancer: Nanoparticles Turn Immune System Soldiers Against Tumor Cells. ScienceDaily. Retrieved March 30, 2015 from www.sciencedaily.com/releases/2009/07/090715160821.htm
Dartmouth-Hitchcock Medical Center. "Trojan Horse For Ovarian Cancer: Nanoparticles Turn Immune System Soldiers Against Tumor Cells." ScienceDaily. www.sciencedaily.com/releases/2009/07/090715160821.htm (accessed March 30, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, March 30, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Soda, Salt and Sugar: The Next Generation of Taxes

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015) — Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline. Video provided by Washington Post
Powered by NewsLook.com
UnitedHealth Buys Catamaran

UnitedHealth Buys Catamaran

Reuters - Business Video Online (Mar. 30, 2015) — The $12.8 billion merger will combine the U.S.&apos; third and fourth largest pharmacy benefit managers. Analysts say smaller PBMs could also merge. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
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