- About Us
- Career Center
- Nano-Social Network
- Nano Consulting
- My Account
|Dr. Jose Conejo-Garcia (right) with graduate student Juan Cubillos-Ruiz|
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.
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:
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
Copyright © Dartmouth Medical SchoolIf 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.
|Related News Press|
News and information
Kalam: versatility personified August 1st, 2015
Gold-diamond nanodevice for hyperlocalised cancer therapy: Gold nanorods can be used as remote controlled nanoheaters delivering the right amount of thermal treatment to cancer cells, thanks to diamond nanocrystals used as temperature sensors August 1st, 2015
Take a trip through the brain July 30th, 2015
Sol-gel capacitor dielectric offers record-high energy storage July 30th, 2015
Self-assembling, biomimetic membranes may aid water filtration August 1st, 2015
European Technology Platform for Nanomedicine and ENATRANS European Consortium Launch the 2nd edition of the Nanomedicine Award: The Award to be presented at BIO-Europe conference in Munich, November 2015 July 30th, 2015
New computer model could explain how simple molecules took first step toward life: Two Brookhaven researchers developed theoretical model to explain the origins of self-replicating molecules July 28th, 2015
Spintronics: Molecules stabilizing magnetism: Organic molecules fixing the magnetic orientation of a cobalt surface/ building block for a compact and low-cost storage technology/ publication in Nature Materials July 25th, 2015