Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Nanodrug targeting breast cancer cells from the inside adds weapon: Immune system attack

The multipronged approach directly attacks cancer cells, blocking the growth of cancer-supporting blood vessels and stimulating an antitumor immune response

A unique nanoscale drug that can carry a variety of weapons and sneak into cancer cells to break them down from the inside has a new component: a protein that stimulates the immune system to attack HER2-positive breast cancer cells.

The research team developing the drug – led by scientists at the Nanomedicine Research Center, part of the Maxine Dunitz Neurosurgical Institute in the Department of Neurosurgery at Cedars-Sinai Medical Center – conducted the study in laboratory mice with implanted human breast cancer cells. Mice receiving the drug lived significantly longer than untreated counterparts and those receiving only certain components of the drug, according to a recent article in the Journal of Controlled Release.

Researchers from the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai, the Division of Surgical Oncology at UCLA, and the Molecular Biology Institute at UCLA also participated in the study.

Unlike other drugs that target cancer cells from the outside, often injuring normal cells as a side effect, this therapy consists of multiple drugs chemically bonded to a "nanoplatform" that functions as a transport vehicle.

HER2-positive cancers – making up 25 to 30 percent of breast and ovarian cancers – tend to be more aggressive and less responsive to treatment than others because the overactive HER2 gene makes excessive amounts of a protein that promotes cancer growth. One commonly used drug, Herceptin (trastuzumab), often is effective for a while, but many tumors become resistant within the first year of treatment and the drug can injure normal organs it contacts.

But Herceptin is an antibody to the HER2 gene – it naturally seeks out this protein – so the research team used key parts of Herceptin to guide the nanodrug into HER2-positive cancer cells.

"We genetically prepared a new 'fusion gene' that consists of an immune-stimulating protein, interleukin-2, and a gene of Herceptin," said Julia Y. Ljubimova, MD, PhD, professor of neurosurgery and biomedical sciences and director of the Nanomedicine Research Center. "IL-2 activates a variety of immune cells but is not stable in blood plasma and does not home specifically to tumor cells. By attaching the new fusion antibody to the nanoplatform, we were able to deliver Herceptin directly to HER2-positive cancer cells, at the same time transporting IL-2 to the tumor site to stimulate the immune system. Attaching IL-2 to the platform helped stabilize the protein and allowed us to double the dosage that could be delivered to the tumor."

Ljubimova led the study with Manuel Penichet, MD, PhD, associate professor of surgery, microbiology, immunology and molecular genetics at the University of California, Los Angeles, David Geffen School of Medicine. Ljubimova said the UCLA collaborators developed the fusion gene, and Cedars-Sinai chemists Eggehard Holler, PhD, professor in the Department of Neurosurgery, and Hui Ding, PhD, assistant professor, performed the technically difficult task of attaching it to the nanoplatform. Ding is the journal article's first author.

The researchers also attached other components, such as molecules to block a protein (laminin-411) that cancer cells need to make new blood vessels for growth.

The nanodrug, Polycefin, is in an emerging class called nanobiopolymeric conjugates, nanoconjugates or nanobioconjugates. They are the latest evolution of molecular drugs designed to slow or stop cancers by blocking them in multiple ways. Polycefin is intended to slow their growth by entering cells and altering defined targets. The new version also stimulates the immune system to further weaken cancers.

"We believe this is the first time a drug has been designed for nano-immunology anti-cancer treatment," Ljubimova said.

Bioconjugates are drugs that contain chemical "modules" attached (conjugated) to a delivery vehicle by strong chemical bonds. The nanoconjugate exists as a single chemical unit, and the tight bonds prevent the components from getting damaged or separated in tissues or blood plasma during transit. With inventive drug engineering, the anti-tumor components activate inside tumor cells.

"More study is needed to confirm our findings, improve the effectiveness of this approach and shed light on the anti-cancer mechanisms at work, but it appears that the nanobioconjugate may represent a new generation of cancer therapeutics in which we launch a multipronged attack that directly kills cancer cells, blocks the growth of cancer-supporting blood vessels and stimulates a powerful antitumor immune response," Ljubimova said, adding that this and previous animal studies have found the nanodrug to be a safe and efficient delivery platform.

Nano researchers manipulate substances and materials at the atomic level, generally working with substances smaller than 100 nanometers. Cedars-Sinai's nanoconjugate is estimated to be about 27 nanometers wide. A human hair is 80,000 to 100,000 nanometers wide.

This study was supported in part by grants from the National Institutes of Health/National Cancer Institute (R01CA123459, U01CA151815, R01CA136841, K01CA138559. Additional support came from the UC MEXUS-CONACYT Fellowship Program, the Howard Hughes Medical Institute Gilliam Fellowship, the Whitcome Fellowship of the Molecular Biology Institute at UCLA, ANPCyT-FONARSEC PICT-PRH 2008-00315, the CONICET PIP no. 114-2011-01-00139, and the UBACYT No 200-2011-02-00027. The UCLA Flow Cytometry Core Facility is supported by NIH awards CA16042 and AI28697, the Jonsson Cancer Center, the UCLA AIDS Institute and the UCLA School of Medicine.

Citation: Journal of Controlled Release, "Polymalic acid nanobioconjugate for simultaneous immunostimulation and inhibition of tumor growth in HER2/neu-positive breast cancer"

Sandy Van | Cedars-Sinai News
Further information:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Taming chaos: Calculating probability in complex systems

21.03.2018 | Physics and Astronomy

Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

21.03.2018 | Physics and Astronomy

New 4-D printer could reshape the world we live in

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>