Nanoparticles reprogram immune cells to fight cancer

Dr. Matthias Stephan has a bold vision. He imagines a future where patients with leukemia could be treated as early as the day they are diagnosed with cellular immunotherapy that’s available in their neighborhood clinic and is as simple to administer as today’s chemotherapy, but without the harsh side effects. The key to that scientific leap? Nanoparticles, tiny technology that’s able to carry tumor-targeting genes directly to immune cells still within the body and program them to destroy cancer. In a proof-of-principle study published Monday in Nature Nanotechnology, Stephan and other researchers at Fred Hutchinson Cancer Research Center showed that nanoparticle-programmed immune cells, known as T cells, can clear or slow the progression of leukemia in a preclinical model.

nanoparticles reprogram genes

“Our technology is the first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Stephan, the study’s senior author. Although his method for programming T cells is still several steps away from the clinic, Stephan envisions a future in which biodegradable nanoparticles could transform cell-based immunotherapies — whether for cancer or infectious disease — into an easily administered, off-the-shelf treatment that’s available anywhere.

Stephan imagines that in the future, nanoparticle-based immunotherapy could be “something that is available right away and can hopefully out-compete chemotherapies. That’s my excitement.”

Source: https://www.fredhutch.org/

Nanoparticles And Immunotherapy, Allies To Eradicate Cancer

Some researchers are working to discover new, safer ways to deliver cancer-fighting drugs to tumors without damaging healthy cells. Others are finding ways to boost the body’s own immune system to attack cancer cells. Researchers at Pennsylvania State University   (Penn State) have combined the two approaches by taking biodegradable polymer nanoparticles encapsulated with cancer-fighting drugs and incorporating them into immune cells to create a smart, targeted system to attack cancers of specific types.

new-anti-cancer-drugs

The traditional way to deliver drugs to tumors is to put the drug inside some type of nanoparticle and inject those particles into the bloodstream,” said Jian Yang, professor of biomedical engineering, Penn State. “Because the particles are so small, if they happen to reach the tumor site they have a chance of penetrating through the blood vessel wall because the vasculature of tumors is usually leaky.”

The odds of interacting with cancer cells can be improved by coating the outside of the nanoparticles with antibodies or certain proteins or peptides that will lock onto the cancer cell when they make contact. However, this is still a passive drug delivery technology. If the particle does not go to the tumor, there is no chance for it to bind and deliver the drug.

Yang and Cheng Dong, professor of biomedical engineering, wanted a more active method of sending drugs to the cancer wherever it was located, whether circulating in the blood, the brain, or any of the other organs of the body.

“I have 10 years of working in immunology and cancer,” Dong said. “Jian is more a biomaterials scientist. He knows how to make the nanoparticles biodegradable. He knows how to modify the particles with surface chemistry, to decorate them with peptides or antibodies. His material is naturally fluorescent, so you can track the particles at the same time they are delivering the drug, a process called theranostics that combines therapy and diagnostics. On the other hand, I study the cancer microenvironment, and I have discovered that the microenvironment of the tumor generates kinds of inflammatory signals similar to what would happen if you had an infection.”

Immune cells, which were built to respond to inflammatory signals, will be naturally attracted to the tumor site. This makes immune cells a perfect active delivery system for Yang’s nanoparticles. The same technology is also likely to be effective for infectious or other diseases, as well as for tissue regeneration, Dong said.

Source: http://news.psu.edu/

How To Stop The Spread Of Breast Cancer

A breakthrough technology that harnesses manmade nanoparticles could one day become an important new weapon in the fight against cancer. The technique, which appeared to successfully stop the spread of breast cancer in mice, was unveiled by scientists from the Cold Spring Harbor Laboratory, Dana-Farber Cancer Institute, Stony Brook University, and a host of other research institutions in the journal Science Translational Medicine.

Next-generation cancer fighting therapies on the market today use the body’s immune system to combat tumors, as does experimental technology like CRISPR gene-editing. But the new nanotech has a different target: The cells that actually help cancer metastasize and spread throughout the body. These immune cells, which are meant to ward off infections, create structures called neutrophil extracellular traps (NETs) that help them fight bacteria. But NETs can actually wind up helping spread the cancer by creating tissue openings that cancerous cells can exploit, study co-author Mikala Egeblad explained.

 breast-cancer-cells

A high magnification of an intact neutrophil (yellow arrow) and a NET (white arrow)

So the researchers created a new particle coated with a special enzyme that can kill these cells before the cancer can use them to metastasize. The results were modest, but promising: Three out of the nine mice given the nanoparticle showed no evidence of breast cancer progression, while all mice in the control group continued to worsen.

Triggered Immune Cells Attack Cancer

Stanford researchers accidentally discovered that iron nanoparticles invented for anemia treatment have another use: triggering the immune system’s ability to destroy tumor cellsIron nanoparticles can activate the immune system to attack cancer cells, according to a study led by researchers at the Stanford University School of Medicine. The nanoparticles, which are commercially available as the injectable iron supplement ferumoxytol, are approved by the Food and Drug Administration (FDA) to treat iron deficiency anemia.

The mouse study found that ferumoxytol prompts immune cells called tumor-associated macrophages to destroy cancer cells, suggesting that the nanoparticles could complement existing cancer treatments.

macrophages-attack-cancerA mouse study found that ferumoxytol prompts immune cells called tumor-associated macrophages to destroy tumor cells.

It was really surprising to us that the nanoparticles activated macrophages so that they started to attack cancer cells in mice,” said Heike Daldrup-Link, MD, who is the study’s senior author and an associate professor of radiology at the School of Medicine. “We think this concept should hold in human patients, too.

The study showed that the iron nanoparticles switch the macrophages back to their cancer-attacking state, as evidenced by tracking the products of the macrophages’ metabolism and examining their patterns of gene expression.

Furthermore, in a mouse model of breast cancer, the researchers demonstrated that the ferumoxytol inhibited tumor growth when given in doses, adjusted for body weight, similar to those approved by the FDA for anemia treatment.

Daldrup-Link’s team conducted an experiment that used three groups of mice: an experimental group that got nanoparticles loaded with chemo, a control group that got nanoparticles without chemo and a control group that got neither. The researchers made the unexpected observation that the growth of the tumors in control animals that got nanoparticles only was suppressed compared with the other controls.

The discovery, described in a paper published online in Nature Nanotechnology, was made by accident while testing whether the nanoparticles could serve as Trojan horses by sneaking chemotherapy into tumors in mice.
Source: http://med.stanford.edu/

Trojan Horse Nanoparticles Attack Inflammation

Nanosized Trojan horses created from a patient’s own immune cells have successfully treated inflammation by overcoming the body’s complex defense mechanisms, perhaps leading to broader applications for treating diseases characterized by inflammation, such as cancer and cardiovascular diseases. An international team, led by researchers at Houston Methodist Research Institute, described the creation of nanoparticles called leukosomes and evaluated their ability to treat localized inflammation in the May 23 issue of Nature Materials (early online). Recent approaches to treating inflammatory diseases have been unsuccessful because an already overactive immune system treats simple nanoparticles as foreign invaders and clears them from the body, preventing them from reaching their target.
tissue inflammation2A better approach for building effective drug delivery platforms is to find inspiration for their design in the composition of the immune cells of our body,” said Ennio Tasciotti, Ph.D., director of the Center for Biomimetic Medicine at Houston Methodist Research Institute and the paper’s senior author.
Immune cells such as leukocytes freely circulate in blood vessels, recognize inflammation, and accumulate in inflamed tissues. They do so by using special receptors and ligands on their surface. We purified leukocytes from a patient, then integrated their special ligands and receptors into the leukosome surface. Using the body’s own materials, we built a drug delivery system camouflaged as our own body’s defense system—thus the Trojan horse.

Source: http://www.houstonmethodist.org/

Possible Soft Cure For Inflammatory Bowel Disease

Nanoparticles designed to block a cell-surface molecule that plays a key role in inflammation could be a safe treatment for inflammatory bowel disease (IBD), according to researchers in the Institute for Biomedical Sciences at Georgia State University and Southwest University in China. The scientists developed nanoparticles, or microscopic particles, to reduce the expression of  CD98, a glycoprotein that promotes inflammation.

IBD

Our results suggest this nanoparticle could potentially be used as an efficient therapeutic treatment for inflammation,” said Didier Merlin, professor in the Institute for Biomedical Sciences at Georgia State and researcher at the Atlanta Veterans Affairs Medical Center.

We targeted CD98 because we determined in a previous study that CD98 is highly over-expressed in activated immune cells involved in IBD.”

In the United States, as many as 1.3 million people suffer from IBD, which includes ulcerative colitis and Crohn’s disease, conditions with chronic or recurring abnormal response to the body’s immune system and inflammation of the gastrointestinal tract. IBD gets worse over time and causes severe gastrointestinal symptoms, such as persistent diarrhea, cramping abdominal pain, fever, rectal bleeding, loss of appetite and weight loss. Surgery is required when medication can no longer control the symptoms, and patients also have an increased risk of colon cancer, according to the Centers for Disease Control and Prevention.

This study suggests the development of nanotherapeutic strategies could be an alternative to currently available drugs, which are limited by serious side effects, in treating inflammatory conditions such as IBD.

The findings are published in the journal Colloids and Surfaces B: Biointerfaces.

Source: http://news.gsu.edu/

Vaccine For Type 1 Diabetes?

New findings suggesting that children diagnosed with type 1 diabetes before the age of seven have a very different form of the disease could lead to new ways of treating it, potentially including a vaccine. Nine year old Bethan has Type 1 diabetes. She uses an omnipod pump to deliver insulin when required, while Mum Lizzie watches her diet. Before her diagnosis, life was tough.


type1 diabetes
I felt very weak and tired all the time“complains BethanWestcott-Storer, the nine-year old Diabetes type 1 patient.

Her mother comments: “We noticed that she’d become quite thin, she’d lost a lot of weight, but she didn’t have all of the signs that other children normally have with type 1 – she didn’t have the excess thirst and urinating. Just lost a lot of weight, so she’s been diagnosed for 15 months now.”
Now Bethan’s the picture of health…and the news could get better. The University of Exeter Medical School (UK)  has made a major discovery that could lead to better treatment and even prevention of the disease.

It’s always been thought that when people get type 1 diabetes they’ve lost as many as 90 percent of their insulin producing cells from their pancreas. What we’ve found is that while that might be the case for the younger children it certainly doesn’t appear to be true for those that are older. They have quite a considerable reserve of cells left. That’s a new insight and it might mean that if we could reactivate those cells we could help them to cope better with their illness.“, says Prof. Noel Morgan, of the University of Exeter Medical School.

Researchers examined around 100 pancreas samples in Exeter‘s biobank. They found that those diagnosed before the age of seven develop a more aggressive form of the disease than teenagers.

Those samples are extremely important because we do not understand the underlying disease process that goes on in these individuals and it’s that recent diagnosis that’s critical for us to actually look inside the pancreas and see what is going wrong, and the pancreas itself is an extremely inaccessible organ“, says Dr. Sarah Richardson, from the University of Exeter Medical School. “We’re trying to understand what the trigger is and it may be possible to use a vaccine to stop the triggering process, but it might also be able to use a different kind of vaccine to target the specific immune cells that are causing the illness, and that’s where the excitement lies“, adds Prof.  Morgan. Although well adjusted to her daily routine, Bethan also has high hopes for the ongoing research: “If one day in the future they find a cure or something lots and lots of people are going to be really happy“!

Source: http://www.reuters.com/

Nanotherapy Against Myeloma

Researchers at Washington University School of Medicine in St. Louis have developed a nanotherapy that is effective in treating mice with multiple myeloma, a cancer of bone marrow immune cells.
Multiple myeloma is a cancer that affects plasma cells. These cells are part of the immune system, manufacturing antibodies that fight off infection. But in multiple myeloma, plasma cells grow out of control in the bone marrow, crowding out healthy cells. While treatments exist, only about 50 percent of patients with the disease survive five years past diagnosis.
Targeted specifically to the malignant cells, these new nanoparticles protect their therapeutic cargo from degradation in the bloodstream and greatly enhance drug delivery into the cancer cells. These are longtime hurdles in the development of this class of potential cancer drugs.

Plasmacytoma“We’re excited about our results because there was no guarantee the nanotherapy would increase survival,” said oncologist Michael H. Tomasson, MD, associate professor of medicine. “We injected the nanoparticles intravenously, and they found the tumors throughout the body, whether they were in the bone marrow, the spleen or elsewhere.”

The nanoparticles carry a drug compound that blocks a protein called Myc that is active in many types of cancer, including multiple myeloma. So-called Myc inhibitors are extremely potent in a petri dish. But when injected into the blood, they degrade immediately. Consequently, the prospect that Myc inhibitors could be a viable treatment in patients has been problematic because past research in animals has shown that the compounds degrade too quickly to have any effect against cancer.

The new study is the first to show that Myc inhibitors can be effective in animals with cancer, as long as the drugs have a vehicle to protect and deliver them into cancer cells. When injected into mice with multiple myeloma, the targeted nanoparticles carrying the Myc inhibitor increased survival to 52 days compared with 29 days for mice receiving nanoparticles not carrying the drug.

The study appears online in the journal Molecular Cancer Therapy.

Source: https://news.wustl.edu/

Stealth Nanoparticles Vaccines To Attack Cancer

Cancer vaccines have recently emerged as a promising approach for killing tumor cells before they spread. But so far, most clinical candidates haven’t worked that well. Now, scientists from Department of Immuno-Gene Therapy, Mie University – Japan – have developed a new way to deliver vaccines that successfully stifled tumor growth when tested in laboratory mice. And the key, they report in the journal ACS Nano, is in the vaccine’s unique stealthy nanoparticles. Hiroshi Shiku, Naozumi Harada and colleagues explain that most cancer vaccine candidates are designed to flag down immune cells, called macrophages and dendritic cells, that signal “killerT cells to attack tumors.

immuneCellsGetting immune cells (blue) to kill cancer cells (yellow) could require a stealthy approach.
The problem is that approaches based on targeting these generally circulating immune cells have not been very successful. But recent research has suggested that a subset of macrophages only found deep inside lymph nodes could play a major role in slowing cancer. But how could one get a vaccine to these special immune cells without first being gobbled up by the macrophages and dendritic cells circulating in the body? Shiku’s team wanted to see if stealthy nanoparticles they had developed and clinically tested in patients might hold the answer.
Source: http://www.acs.org/

Cancer: How To Boost Immune Cells

Scientists at Yale University have developed a novel cancer immunotherapy that rapidly grows and enhances a patient’s immune cells outside the body using carbon nanotube-polymer composites; the immune cells can then be injected back into a patient’s blood to boost the immune response or fight cancer.

The researchers used bundled carbon nanotubes (CNTs) to incubate cytotoxic T cells, a type of white blood cell that is important to immune system functions. According to the researchers, the topography of the CNTs enhances interactions between cells and long-term cultures, providing a fast and effective stimulation of the cytotoxic T cells that are important for eradicating cancer.

cancer-helfA high-resolution, scanning electron microscope image of the carbon nanotube-polymer composite. The bundled CNTs appear as spaghetti-like structures.
In repressing the body’s immune response, tumors are like a castle with a moat around it,” says Tarek Fahmy, an associate professor of biomedical engineering and the study’s principal investigator. “Our method recruits significantly more cells to the battle and arms them to become superkillers.”
The findings ae reported Aug. 3 in Nature Nanotechnology.

Source: http://news.yale.edu/

How To Track Proteins In HIV Particle

An interdisciplinary team of scientists from KU Leuven in Belgium has developed a new technique to examine how proteins interact with each other at the level of a single HIV viral particle. The technique allows scientists to study the life-threatening virus in detail and makes screening potential anti-HIV drugs quicker and more efficient. The technique can also be used to study other diseases.


Essentially, we have created a nano test tube out of an HIV virion, inside of which protein interactions can be studied,” says co-author Jelle Hendrix.
Understanding how the human immunodeficiency virus (HIV) reproduces itself is crucial in the effort to fight the disease. Upon entering the bloodstream, HIV viral particles, or virions, ‘highjack’ individual immune cells. The virion binds to and then penetrates the immune cell. Once inside, the virion reprograms the genetic material of the immune cell to produce more HIV virions. In this way, HIV disables the diseasefighting ‘bodyguards’ in our blood and turns them into breeding machines for new HIV virions.

Source: http://www.kuleuven.be/

Nanoparticles Reprogram Immune Cells To Attack Cancer

Researchers at the University of Georgia are developing a new treatment technique that uses nanoparticles to reprogram immune cells so they are able to recognize and attack cancer.
The human body operates under a constant state of martial law. Chief among the enforcers charged with maintaining order is the immune system, a complex network that seeks out and destroys the hordes of invading bacteria and viruses that threaten the organic society as it goes about its work. The immune system is good at its job, but it’s not perfect. Most cancerous cells, for example, are able to avoid detection by the immune system because they so closely resemble normal cells, leaving the cancerous cells free to multiply and grow into life-threatening tumors while the body’s only protectors remain unaware. Shanta Dhar and her colleagues are giving the immune system a boost through their research.

immunity and cancer

What we are working on is specifically geared toward breast cancer,” said Dhar, the study’s co-author and an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences. “Our paper reports for the first time that we can stimulate the immune system against breast cancer cells using mitochondria-targeted nanoparticles and light using a novel pathway.

The findings were published recently in the early online edition of ACS Nano.
Source: http://news.uga.edu/