Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

Home > Press > Trojan Horse for Ovarian Cancer--Nanoparticles Turn Immune System Soldiers against Tumor Cells

Dr. Jose Conejo-Garcia (right) with graduate student Juan Cubillos-Ruiz
Dr. Jose Conejo-Garcia (right) with graduate student Juan Cubillos-Ruiz

Abstract:
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.

Trojan Horse for Ovarian Cancer--Nanoparticles Turn Immune System Soldiers against Tumor Cells

Hanover, NH | Posted on July 14th, 2009

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, 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.

Read an interview of Jose Conejo - Garcia with the Ovarian Cancer Research Fund, here:
www.ocrf.org/index.php?option=com_content&view=article&id=538:qaa-with-jose-conejo-garcia-md-phd&catid=61:ceo-blog&Itemid=131

####

About Dartmouth Medical School
Dartmouth Medical School is a beacon of discovery and learning, stimulating inquiry and harnessing ingenuity for new solutions and better health. Building on a legacy of excellence and collaboration, DMS, the nation's fourth-oldest medical school, cultivates leaders of vision and virtuosity who are transcending boundaries to transform medicine and science. It draws on the world-class resources of Dartmouth College and Dartmouth-Hitchcock Medical Center for broad interdisciplinary programs in biomedical research, education, patient care and service.

For more information, please click here

Contacts:

603-650-1492

Copyright © Dartmouth Medical School

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Keeping electric car design on the right road: A closer look at the life-cycle impacts of lithium-ion batteries and proton exchange membrane fuel cells December 9th, 2016

Further improvement of qubit lifetime for quantum computers: New technique removes quasiparticles from superconducting quantum circuits December 9th, 2016

Chemical trickery corrals 'hyperactive' metal-oxide cluster December 8th, 2016

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D: Up-close, real-time, chemical-sensitive 3-D imaging offers clues for reducing cost/improving performance of catalysts for fuel-cell-powered vehicles and other applications December 8th, 2016

Possible Futures

Keeping electric car design on the right road: A closer look at the life-cycle impacts of lithium-ion batteries and proton exchange membrane fuel cells December 9th, 2016

Further improvement of qubit lifetime for quantum computers: New technique removes quasiparticles from superconducting quantum circuits December 9th, 2016

Researchers peer into atom-sized tunnels in hunt for better battery: May improve lithium ion for larger devices, like cars December 8th, 2016

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D: Up-close, real-time, chemical-sensitive 3-D imaging offers clues for reducing cost/improving performance of catalysts for fuel-cell-powered vehicles and other applications December 8th, 2016

Nanomedicine

Arrowhead Pharmaceuticals to Webcast Fiscal 2016 Year End Results December 7th, 2016

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Journal Nanotechnology Progress International (JONPI) Volume 6, issue 2 coming out soon! December 5th, 2016

UTSA study describes new minimally invasive device to treat cancer and other illnesses: Medicine diffusion capsule could locally treat multiple ailments and diseases over several weeks December 3rd, 2016

Announcements

Keeping electric car design on the right road: A closer look at the life-cycle impacts of lithium-ion batteries and proton exchange membrane fuel cells December 9th, 2016

Further improvement of qubit lifetime for quantum computers: New technique removes quasiparticles from superconducting quantum circuits December 9th, 2016

Researchers peer into atom-sized tunnels in hunt for better battery: May improve lithium ion for larger devices, like cars December 8th, 2016

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D: Up-close, real-time, chemical-sensitive 3-D imaging offers clues for reducing cost/improving performance of catalysts for fuel-cell-powered vehicles and other applications December 8th, 2016

Nanobiotechnology

Arrowhead Pharmaceuticals to Webcast Fiscal 2016 Year End Results December 7th, 2016

Fast, efficient sperm tails inspire nanobiotechnology December 5th, 2016

Deep insights from surface reactions: Researchers use Stampede supercomputer to study new chemical sensing methods, desalination and bacterial energy production December 2nd, 2016

Nanobiotix Provides Update on Global Development of Lead Product NBTXR3: Seven clinical trials across the world: More than 2/3 of STS patients recruited in the “act.in.sarc” Phase II/III trial: Phase I/II prostate cancer trial now recruiting in the U.S. November 28th, 2016

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project