Nanoparticle Shrinks Breast Tumor, Prevent Recurrence

A Mayo Clinic research team has developed a new type of cancer-fighting nanoparticle aimed at shrinking breast cancer tumors, while also preventing recurrence of the disease. A mice that received an injection with the nanoparticle showed a 70 to 80 percent reduction in tumor size. Most significantly, mice treated with these nanoparticles showed resistance to future tumor recurrence, even when exposed to cancer cells a month later.

The results show that the newly designed nanoparticle produced potent anti-tumor immune responses to HER2-positive breast cancers. Breast cancers with higher levels of HER2 protein are known to grow aggressively and spread more quickly than those without the mutation.

In this proof-of-concept study, we were astounded to find that the animals treated with these nanoparticles showed a lasting anti-cancer effect,” says Betty Y.S. Kim, M.D., Ph.D., principal investigator, and a neurosurgeon and neuroscientist who specializes in brain tumors at Mayo Clinic’s Florida campus. “Unlike existing cancer immunotherapies that target only a portion of the immune system, our custom-designed nanomaterials actively engage the entire immune system to kill cancer cells, prompting the body to create its own memory system to minimize tumor recurrence. These nanomedicines can be expanded to target different types of cancer and other human diseases, including neurovascular and neurodegenerative disorders.”

Dr. Kim’s team developed the nanoparticle, which she has named “Multivalent Bi-specific Nano-Bioconjugate Engager,” a patented technology with Mayo Clinic Ventures, a commercialization arm of Mayo Clinic.

The findings have been published in Nature Nanotechnology.

Source: https://newsnetwork.mayoclinic.org/

Nanoparticle Vaccine Against Cancer

Researchers from UT Southwestern Medical Center have developed a first-of-its-kind nanoparticle vaccine immunotherapy that targets several different cancer types.

The nanovaccine consists of tumor antigens tumor proteins that can be recognized by the immune system – inside a synthetic polymer nanoparticle. Nanoparticle vaccines deliver minuscule particulates that stimulate the immune system to mount an immune response. The goal is to help people’s own bodies fight cancer.


cancer-cells-

What is unique about our design is the simplicity of the single-polymer composition that can precisely deliver tumor antigens to immune cells while stimulating innate immunity. These actions result in safe and robust production of tumor-specific T cells that kill cancer cells,” said Dr. Jinming Gao, a Professor of Pharmacology and Otolaryngology in UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center.

A study outlining this research, published online today in Nature Nanotechnology, reported that the nanovaccine had anti-tumor efficacy in multiple tumor types in mice.

The research was a collaboration between the laboratories of study senior authors Dr. Gao and Dr. Zhijian “James” Chen, Professor of Molecular Biology and Director of the Center for Inflammation Research. The Center was established in 2015 to study how the body senses infection and to develop approaches to exploit this knowledge to create new treatments for infection, immune disorders, and autoimmunity.

Source: http://www.utsouthwestern.edu/

‘Protective’ DNA strands are shorter in adults who had more infections as infants

New research indicates that people who had more infections as babies harbor a key marker of cellular aging as young adults: the protective stretches of DNA which “cap” the ends of their chromosomes are shorter than in adults who were healthier as infants.

TELOMERESThe 46 chromosomes of the human genome, with telomeres highlighted in white

These are important and surprising findings because — generally speaking — shorter chromosome ‘caps’ are associated with a higher burden of disease later in life,” said lead author Dan Eisenberg, an assistant professor of anthropology at the University of Washington.

The ‘caps’ Eisenberg and his co-authors measured are called telomeres. These are long stretches of DNA at the ends of our chromosomes, which protect our genes from damage or improper regulation. One Nobel Prize-winning scientist who studies telomeres has compared them to aglets — the plastic or metal sheath covering ends of shoelaces. When aglets wear down, the shoelace is exposed to fraying and degradation from environmental forces.

Like aglets, telomeres don’t last forever. In most of our cells, telomeres get shorter each time that cell divides. And when they get too short, the cell either quits dividing or dies.

That makes telomere length particularly important for the cells of our immune system, especially the white blood cells circulating in our bloodstream. When activated against a pathogen, white blood cells undergo rapid rounds of cell division to raise a defensive force against the infectious invader. But if telomeres in white blood cells are already too short, the body may struggle to mount an effective immune response.

Many studies — in laboratory animals and humans — have associated shorter telomeres with poor health outcomes, especially in adults,” said Eisenberg. But few studies have addressed whether or not events early in a person’s life might affect telomere length. To get at this question, Eisenberg turned to the Cebu Longitudinal Health and Nutrition Survey, which has tracked the health of over 3,000 infants born in 1983-1984 in Cebu City in the Philippines. Researchers collected detailed data every two months from mothers on the health and feeding habits of their babies up through age two. Mothers reported how often their babies had diarrhea — a sign of infection — as well as how often they breastfed their babies. As these babies grew up, scientists collected additional health data during follow-up surveys over the next 20 years. In 2005, 1,776 of these offspring donated a blood sample. By then, they were 21- or 22-year-old young adults.

Eisenberg measured telomere length in cells from those blood samples. He then combined the data on adult telomere length with information about their health and feeding habits as babies. He found that babies with higher reported cases of diarrhea at 6 to 12 months also had the shortest telomeres as adults.

The findings have been published in the American Journal of Human Biology.

Source: http://www.washington.edu/

Nanoparticles Trigger Dormant Viruses In Lung Cells

Nanoparticles from combustion engines can activate viruses that are dormant in lung tissue cells. This is the result of a study by researchers of Helmholtz Zentrum München, a partner in the German Center for Lung Research (DZL), which has now been published in the journal ‘Particle and Fibre Toxicology‘.

To evade the immune system, some viruses hide in cells of their host and persist there. In medical terminology, this state is referred to as a latent infection. If the immune system becomes weakened or if certain conditions change, the viruses become active again, begin to proliferate and destroy the host cell. A team of scientists led by Dr. Tobias Stöger of the Institute of Lung Biology and Prof. Dr. Heiko Adler, deputy head of the research unit Lung Repair and Regeneration at Helmholtz Zentrum München, now report that nanoparticles can also trigger this process.

car engine nanoparticles

From previous model studies we already knew that the inhalation of nanoparticles has an inflammatory effect and alters the immune system,” said study leader Stöger. Together with his colleagues Heiko Adler and Prof. Dr. Philippe Schmitt-Kopplin, he showed that “an exposure to nanoparticles can reactivate latent herpes viruses in the lung.

Source: https://www.helmholtz-muenchen.de/

ImmunoTherapy Registers Success Against Brain Cancer

Using the immune system to beat cancer is quickly becoming a promising new strategy for battling tumors. But most of the success so far has been with blood cancers like lymphomas and leukemias. Immunotherapy, as it’s called, has yet to prove itself with solid tumors like breast, prostate, lung, colon and brain cancers.But in a report published in the New England Journal of Medicine, researchers led by Dr. Behnam Badie from the City of Hope Beckman Research Institute and Medical Center say that the same immune-based therapy that is successful against blood cancers also helped a patient with advanced brain cancer.

brain cancer

The 50-year-old man with glioblastoma, a particularly aggressive type of brain tumor, had already been treated with surgery, radiation and anti-tumor drug therapies. Despite these treatments, his cancer had returned and also spread to other parts of his brain and spinal cord. Badie and his team extracted immune cells from him, then engineered them to express proteins on their surface that would recognize and destroy glioblastoma tumor cells. After surgery to remove the bulk of the brain tumor, Badie and his colleagues directly injected the site with the modified immune cells (called chimeric antigen receptor T cells, or CAR T cells) six times, and the remaining part of this tumor stopped growing.

Other smaller growths in the brain continued to grow, however, so the patient received 10 more doses of the CAR T cells injected into the cavities in the brain, called the ventricles. This is the first time that immune cells have been injected into these brain regions, because introducing anything into the ventricles can cause dangerous and possibly deadly inflammation. The man did not develop such serious complications, however, and after about four months, these tumors too started to shrink. By six months, almost all had disappeared.

If the patient had not received the CAR T therapy, he likely would only have survived a few weeks after his cancer recurred, says Badie. But after being treated with the immune therapy, his cancer did not grow or recur for nearly eight months. “If we can do the same for other patients, that would be an amazing accomplishment that many decades of work and research on glioblastoma have never done,” says Badie, whose own father passed away a decade ago from glioblastoma.

Source: http://time.com/

Tatoo Therapy

A temporary tattoo to help control a chronic disease might someday be possible, according to scientists at Baylor College of Medicine who tested antioxidant nanoparticles created at Rice University. A proof-of-principle study led by Baylor scientist Christine Beeton published by Nature’s online, open-access journal Scientific Reports shows that nanoparticles modified with polyethylene glycol are conveniently choosy as they are taken up by cells in the immune system. That could be a plus for patients with autoimmune diseases like multiple sclerosis, one focus of study at the Beeton lab.

tatoo-therapy

“Placed just under the skin, the carbon-based particles form a dark spot that fades over about one week as they are slowly released into the circulation,” Beeton said. T and B lymphocyte cells and macrophages are key components of the immune system. However, in many autoimmune diseases such as multiple sclerosis, T cells are the key players. One suspected cause is that T cells lose their ability to distinguish between invaders and healthy tissue and attack both.

In tests at Baylor, nanoparticles were internalized by T cells, which inhibited their function, but ignored by macrophages. “The ability to selectively inhibit one type of cell over others in the same environment may help doctors gain more control over autoimmune diseases,” Beeton said. “The majority of current treatments are general, broad-spectrum immunosuppressants,” said Redwan Huq, lead author of the study and a graduate student in the Beeton lab. “They’re going to affect all of these cells, but patients are exposed to side effects (ranging) from infections to increased chances of developing cancer. So we get excited when we see something new that could potentially enable selectivity.” Since the macrophages and other splenic immune cells are unaffected, most of a patient’s existing immune system remains intact, he added.

 

Source: http://news.rice.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/

Nanoparticles Trigger Immune System To Destroy Cancer

The shells of a common plant virus, inhaled into a lung tumor or injected into ovarian, colon or breast tumors, not only triggered the immune system in mice to wipe out the tumors, but provided systemic protection against metastases, researchers from Case Western Reserve University and Dartmouth University report. The scientists tested a 100-year-old idea called in-situ vaccination. The idea is to put something inside a tumor and disrupt the environment that suppresses the immune system, thus allowing the natural defense system to attack the malignancy.

That something—the hard coating of cowpea* mosaic virus—caused no detectible side effects, which are a common problem with traditional therapies and some immunotherapies.

cowpeas

The cowpea virus-based nanoparticles act like a switch that turns on the immune system to recognize and fight against the tumor – as well as to remember it,” said Nicole Steinmetz, an assistant professor of biomedical engineering at Case Western Reserve, appointed by the Case Western Reserve School of Medicine.

The particles are shockingly potent,” said Steven Fiering, professor of microbiology and immunology at Dartmouth’s Geisel School of Medicine. “They’re easy to make and don’t need to carry antigens, drugs or other immunostimmulatory agents on their surface or inside.”

The team’s research is published in the journal Nature Nanotechnology.

* Cowpeas are one of the most important food legume crops in the semiarid tropics covering Asia, Africa, southern Europe, and Central and South America

Source: http://blog.case.edu/

How to Make Carbon Nanoparticles In Your Kitchen

Researchers led by University of Illinois bioengineering professors Dipanjan Pan and Rohit Bhargava, have found an easy way to produce carbon nanoparticles that are small enough to evade the body’s immune system, reflect light in the near-infrared range for easy detection, and carry payloads of pharmaceutical drugs to targeted tissues. Unlike other methods of making carbon nanoparticles – which require expensive equipment and purification processes that can take days – the new approach generates the particles in a few hours and uses only a handful of ingredients, including store-bought molasses.


nanoparticles-300x225

If you have a microwave and honey or molasses, you can pretty much make these particles at home,” Pan said. “You just mix them together and cook it for a few minutes, and you get something that looks like char, but that is nanoparticles with high luminescence. This is one of the simplest systems that we can think of. It is safe and highly scalable for eventual clinical use.

These “next-generation” carbon spheres have several attractive properties, the researchers found. They naturally scatter light in a manner that makes them easy to differentiate from human tissues, eliminating the need for added dyes or fluorescing molecules to help detect them in the body.

The nanoparticles are coated with polymers that fine-tune their optical properties and their rate of degradation in the body. The polymers can be loaded with drugs that are gradually released.
The nanoparticles also can be made quite small, less than eight nanometers in diameter (a human hair is 80,000 to 100,000 nanometers thick).

Our immune system fails to recognize anything under 10 nanometers,” Pan said. “So, these tiny particles are kind of camouflaged, I would say; they are hiding from the human immune system.

The researchers report their findings in the journal Small.

Source: http://news.illinois.edu/

Injectable 3D Vaccine Fights Cancer and HIV

One of the reasons cancer is so deadly is that it can evade attack from the body’s immune system, which allows tumors to flourish and spread. Scientists can try to induce the immune system, known as immunotherapy, to go into attack mode to fight cancer and to build long lasting immune resistance to cancer cells. Now, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard’s School of Engineering and Applied Sciences (SEAS) show a non–surgical injection of programmable biomaterial that spontaneously assembles in vivo into a 3D structure could fight and even help prevent cancer and also infectious disease such as HIV. Their findings are reported in Nature Biotechnology.

dentritic cells
A microscope image shows many of the immune system’s dendritic cells that were collected from a 3D scaffold three days after in vivo injection. The 3D scaffold effectively recruits and activates the dendritic cells to trigger an immune response against specific cells, such as cancerous cells

We can create 3D structures using minimally–invasive delivery to enrich and activate a host’s immune cells to target and attack harmful cells in vivo,” said the study’s senior author David Mooney, Ph.D., who is a Wyss Institute Core Faculty member and the Robert P. Pinkas Professor of Bioengineering at Harvard SEAS. “Nano–sized mesoporous silica particles have already been established as useful for manipulating individual cells from the inside, but this is the first time that larger particles, in the micron–sized range, are used to create a 3D in vivo scaffold that can recruit and attract tens of millions of immune cells,” said co-lead author Jaeyun Kim, Ph.D., an Assistant Professor of Chemical Engineering at Sungkyunkwan University (Korea) and a former Wyss Institute Postdoctoral Fellow.
Source: http://wyss.harvard.edu/

How To Awake The Immune System Against Cancer

Researchers at Dartmouth-Hitchcock Norris Cotton Cancer Center are exploring ways to wake up the immune system so it recognizes and attacks invading cancer cells. Tumors protect themselves by tricking the immune system into accepting everything as normal, even while cancer cells are dividing and spreading.
The immune therapy methods limit a tumor’s ability to trick the immune system. It helps it to recognize the threat and equip it to effectively attack the tumor with more “soldiercells. These approaches are still early in development in the laboratory or clinical trials.

Immune-CellsLeft: A T-cell (orange) kills a cancer cell (mauve). Right: Scanning electron micrograph of a human T-cell. Memory T-cells respond to fight specific pathogens
Our lab’s approach differs from most in that we use nanoparticles to stimulate the immune system to attack tumors and there are a variety of potential ways that can be done,” said Steve Fiering, PhD, Norris Cotton Cancer Center researcher and professor of Microbiology and Immunology, and of Genetics at the Geisel School of Medicine at Dartmouth. “Perhaps the most exciting potential of nanoparticles is that although very small, they can combine multiple therapeutic agents.”
Now that efforts to stimulate anti-tumor immune responses are moving from the lab to the clinic, the potential for nanoparticles to be utilized to improve an immune-based therapy approach is attracting a lot of attention from both scientists and clinicians. And clinical usage does not appear too distant,” said Fiering.

Source: http://cancer.dartmouth.edu/

Very Efficient Dust-Mite Allergy Vaccine

If you’re allergic to dust mites (and chances are you are), help may be on the way.
Researchers at the University of Iowa (UI) have developed a vaccine that can combat dust-mite allergies by naturally switching the body’s immune response. In animal tests, the nano-sized vaccine package lowered lung inflammation by 83 percent despite repeated exposure to the allergens, according to the paper, published in the AAPS (American Association of Pharmaceutical Scientists) Journal. One big reason why it works, the researchers contend, is because the vaccine package contains a booster that alters the body’s inflammatory response to dust-mite allergens.
Allergy1
What is new about this is we have developed a vaccine against dust-mite allergens that hasn’t been used before,” says Aliasger Salem, professor in pharmaceutical sciences at the UI and a corresponding author on the paper.
Dust mites are ubiquitous, microscopic buggers who burrow in mattresses, sofas, and other homey spots. They are found in 84 percent of households in the United States, according to a published, national survey. Preying on skin cells on the body, the mites trigger allergies and breathing difficulties among 45 percent of those who suffer from asthma, according to some studies. Prolonged exposure can cause lung damage.
Usual treatment is limited to getting temporary relief from inhalers or undergoing regular exposure to build up tolerance, which is long term and holds no guarantee of success.
Our research explores a novel approach to treating mite allergy in which specially-encapsulated miniscule particles are administered with sequences of bacterial DNA that direct the immune system to suppress allergic immune responses,” says Peter Thorne, public health professor at the UI and a contributing author on the paper. “This work suggests a way forward to alleviate mite-induced asthma in allergy sufferers.”

Source: http://now.uiowa.edu/