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/

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/

How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”

Source: http://news.psu.edu/

New Technique Identifies Cancer In Urine Or Blood

A team of researchers, led by Professor Yoon-Kyoung Cho of Life Science at UNIST  (South Korea) has recently developed a new technique that effectively identifies cancer-causing substances in the urine or blood.

In the study, Professor Yoon-Kyoung Cho of Life Science, a group leader at IBS Research Center for Soft and Living Matter (CSLM) presented an integrated centrifugal microfluidic platform (Exodisc), a device that isolates extracellular vesicles (EVs) from urine.  The research team expects that this may be potentially useful in clinical settings to test urinary EV-based biomarkers for cancer diagnostics.

Extracellular vesicles (EVs) are cell-derived nanovesicles (40-1000 nm in size), present in almost all types of body fluids, which play a vital role in intercellular communication and are involved in the transport of biological signals for regulating diverse cellular functions. Despite the increasing clinical importance of EVs as potential biomarkers in the diagnosis and prognosis of various diseases, current methods of EV isolation and analysis suffer from complicated procedures with long processing times. For instance, even ultracentrifugation (UC), the most commonly used method for EV isolation, requires time-consuming steps involving centrifugation and acquisition of large sample volumes, and the results suffer from low yield and purity.

To overcome these limitations, Professor Cho presented a new lab-on-a-disc platform for rapid, size-selective, and efficient isolation and analysis of nanoscale EVs from raw biological samples, such as cell-culture supernatant (CCS) or cancer-patient urine.

EXODISC

The Exodisc is compoased of two independent filteration units (20nm and 600nm in size) within a disk-shaped chip to enable the processing of two different samples simulateously,” says Hyun-Kyung Woo (Combined M.S./Ph.D. student of Natural Science), the first author of the study. “Upon spinning the disc, the urine sample is transferred through two integrated nanofilters, allowing for the enrichment of unirary EVs within the size range of 20 to 600 nm.”
Using Exodisc, it is possible to isolate EVs from raw samples within 30 minutes,” says Professor Cho. “The process of passing the filter through centrifugal force is automatically carried out, effectively recovering the enriched EVs.”

On-disc ELISA using urinary EVs isolated from bladder cancer patients showed high levels of CD9 and CD81 expression, suggesting that this method may be potentially useful in clinical settings to test urinary EV-based biomarkers for cancer diagnostics,” explains Vijaya Sunkara of Life Sciences, the co-first author.
The results of the study has been published in the February issue of ACS Nano journal.

Source: http://news.unist.ac.kr/

Killing Cancer Cells From Inside

Researchers have witnessed – for the first time – cancer cells being targeted and destroyed from the inside, by an organo-metal compound discovered by the University of Warwick (UK). Professor Peter J. Sadler, and his group in the Department of Chemistry, have demonstrated that Organo-Osmium FY26 – which was first discovered at Warwick – kills cancer cells by locating and attacking their weakest part.

osmium compound fy26 in cancer cell
This is the first time that an Osmium-based compound – which is fifty times more active than the current cancer drug cisplatin – has been seen to target the disease. Using the European Synchrotron Radiation Facility (ESRF), researchers analysed the effects of Organo-Osmium FY26 in ovarian cancer cells – detecting emissions of X-ray fluorescent light to track the activity of the compound inside the cells

Looking at sections of cancer cells under nano-focus, it was possible to see an unprecedented level of minute detail. Organelles like mitochondria, which are the ‘powerhouses’ of cells and generate their energy, were detectable. In cancer cells, there are errors and mutations in the DNA of mitochondria, making them very weak and susceptible to attack.

FY26 was found to have positioned itself in the mitochondriaattacking and destroying the vital functions of cancer cells from within, at their weakest point. Researchers were also able to see natural metals which are produced by the body – such as zinc and calcium – moving around the cells. Calcium in particular is known to affect the function of cells, and it is thought that this naturally-produced metal helps FY26 to achieve an optimal position for attacking cancer.

Source: http://www2.warwick.ac.uk

A ”NaNose” Device Identifies 17 Types Of Diseases With A Single Sniff

The future of early diagnoses of disease could be this simple, according to a team of researchers in Israel. The ‘NaNose‘ as they call it can differentiate between 17 types of diseases with a single sniff identifying so-called smelly compounds in anything from cancers to Parkinson’s.

nanose2CLICK ON THE IMAGE TO ENJOY THE VIDEO

Indeed, what we have found in our most recent research in this regard, that 17 types of disease have 13 common compounds that are found in all different types of disease, but the mixture of the compounds and the composition of these compounds changes from one disease to another disease. And this is what is really unique and what really we expect to see and utilize in order to make the diagnosis from exhaled breat,” says Professor Hossam  Haick ftom the Institute of Technology- Technion.

The NaNose uses “artificially intelligent nanoarraysensors to analyze the data obtained from receptors that “smell” the patient’s breath.

So our main idea is to try an imitate what’s going on in nature. So like we can take a canine, a dog and train it to scent the smell of drugs, of explosives or a missing person, we are trying to do it artificially. And we can do that by using these nano-materials and we build these nano material-based sensors. And of course there are many advantages and one of them of course is going all the way from sensors big as this to really small devices like this that have that have on them eight sensors and which can be incorporated to systems like this, or even smaller,” explains Doctor Yoav Broza from Technion .

Several companies are now trying to commercialize the technology – and encourage its use in healthcare systems… or see it incorporated into your smartphone.

Source: http://www.reuters.com/

Breakthrough In The BioMedical Industry

Polyhedral boranes, or clusters of boron atoms bound to hydrogen atoms, are transforming the biomedical industry. These manmade materials have become the basis for the creation of cancer therapies, enhanced drug delivery and new contrast agents needed for radioimaging and diagnosis. Now, a researcher at the University of Missouri has discovered an entirely new class of materials based on boranes that might have widespread potential applications, including improved diagnostic tools for cancer and other diseases as well as low-cost solar energy cells.

Mark Lee Jr., an assistant professor of chemistry in the MU College of Arts and Science, discovered the new class of hybrid nanomolecules by combining boranes with carbon and hydrogen. Boranes are chemically stable and have been tested at extreme heat of up to 900 degrees Celsius or 1,652 degrees Fahrenheit. It is the thermodynamic stability these molecules exhibit that make them non-toxic and attractive to the biomedical, personal computer and alternative energy industries.
Polyhedral boranes

Despite their stability, we discovered that boranes react with aromatic hydrocarbons at mildly elevated temperatures, replacing many of the hydrogen atoms with rings of carbon,” Lee said. “Polyhedral boranes are incredibly inert, and it is their reaction with aromatic hydrocarbons like benzene that will make them more useful.”

Lee also showed that the attached hydrocarbons communicate with the borane core. “The result is that these new materials are highly fluorescent in solution,” Lee said. “Fluorescence can be used in applications such as bio-imaging agents and organic light-emitting diodes like those in phones or television screens. Solar cells and other alternative energy sources also use fluorescence, so there are many practical uses for these new materials.
The findings have been recently published in the international journal Angewandte Chemie.

Source: http://munews.missouri.edu/

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/

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/

Graphene Detects Early Cancer

What can’t graphene do? You can scratch “detect cancer” off of that list. By interfacing brain cells onto graphene, researchers at the University of Illinois at Chicago (UIC) have shown they can differentiate a single hyperactive cancerous cell from a normal cell, pointing the way to developing a simple, noninvasive tool for early cancer diagnosis.

graphene-cancer-detectionNormal and cancerous brain cells interfaced with graphene show different activity levels under Raman imaging.
This graphene system is able to detect the level of activity of an interfaced cell,” says Vikas Berry, associate professor and head of chemical engineering at UIC, who led the research along with Ankit Mehta, assistant professor of clinical neurosurgery in the UIC College of Medicine.
The cell’s interface with graphene rearranges the charge distribution in graphene, which modifies the energy of atomic vibration as detected by Raman spectroscopy,” Berry said, referring to a powerful workhorse technique that is routinely used to study graphene. The atomic vibration energy in graphene’s crystal lattice differs depending on whether it’s in contact with a cancer cell or a normal cell, Berry said, because the cancer cell’s hyperactivity leads to a higher negative charge on its surface and the release of more protons.“Graphene is the thinnest known material and is very sensitive to whatever happens on its surface,” Berry said. The nanomaterial is composed of a single layer of carbon atoms linked in a hexagonal chicken-wire pattern, and all the atoms share a cloud of electrons moving freely about the surface.

The study, reported in the journal ACS Applied Materials & Interfaces, looked at cultured human brain cells, comparing normal astrocytes to their cancerous counterpart, the highly malignant brain tumor glioblastoma multiforme. The technique is now being studied in a mouse model of cancer, with results that are “very promising,” Berry said. “Once a patient has brain tumor surgery, we could use this technique to see if the tumor relapses,” Berry said. “For this, we would need a cell sample we could interface with graphene and look to see if cancer cells are still present.”

The same technique may also work to differentiate between other types of cells or the activity of cells. “We may be able to use it with bacteria to quickly see if the strain is Gram-positive or Gram-negative,” Berry said. “We may be able to use it to detect sickle cells.”

Earlier this year, Berry and other coworkers introduced nanoscale ripples in graphene, causing it to conduct differently in perpendicular directions, useful for electronics. They wrinkled the graphene by draping it over a string of rod-shaped bacteria, then vacuum-shrinking the germs. “We took the earlier work and sort of flipped it over,” Berry said. “Instead of laying graphene on cells, we laid cells on graphene and studied graphene’s atomic vibrations.”

Co-authors on the study are Bijentimala Keisham and Phong Nguyen of UIC chemical engineering and Arron Cole of UIC neurosurgery.

Source: https://news.uic.edu/

Immunotherapy Could Eradicate A Third of All Cancers

In August 2015, former US President Jimmy Carter, then 91, announced he had cancer. The diagnosis was metastatic melanoma, and it had spread to his brain. He thought he had merely weeks to live. Just four months later, he made headlines again, revealing he had tested cancer-free. Before long, doctors said he no longer needed treatment. That remarkable turn came from a combination of a traditional therapy, radiation, and a new one, an immunotherapy drug called Keytruda, which was delivered intravenously once every three weeks. Keytruda had only been approved for about a year at that point.

Drug companies see potential for a new group of mega moneymakers. Investors and billionaires, like former New York Mayor Michael Bloomberg and Silicon Valley billionaire Sean Parker, have invested hundreds of millions into researching new treatments. New drugs such as Keytruda are a type of immunotherapy called checkpoint inhibitors. Most people have a type of protein that stops their immune systems from fighting the cancerous cells. Keytruda and similar drugs block those proteins. It’s like taking down a guard tower, allowing the body’s own immune system force to flood past a barrier, where it then gets to work killing and clearing away the cancer cellsCheckpoint inhibitors were first approved to treat melanoma but have since gone on to tackle lung cancer, bladder cancer, blood cancers, and other cancers.

Dan Chen, vice president and global head of cancer immunotherapy development at Genentech considers  checkpoint inhibitor Tecentriq to be the foundation of the company’s cancer immunotherapy program.

cancer-cells

This is a critical program for us. It allowed us to learn an enormous amount about cancer immunity,” like how the drugs work to inhibit the checkpoints, Chen said. Genentech points to patients like Bob Schoenbauer to show why the company is “investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer.”

Schoenbauer had been diagnosed with late-stage inoperable lung cancer in 2013. Soon after, Schoenbauer was connected with a clinical trial of Tecentriq out of Georgetown University. “Almost immediately, the cough was going away,” his wife, Frances, said. “It worked so fast, I couldn’t believe how good he was feeling.” Schoenbauer, who still gets Tecentriq every three weeks, is active and walks to the mall in his Maryland town every morning. He’s in remission.

Still there are some major caveats. First, not everyone is responding to the drugs — for advanced stages of melanoma, the number of people still alive after two years was about 35%, compared to 29.7% over the same time for those taking chemotherapy. And sometimes new checkpoint inhibitors under development fail key trials.

Source: http://uk.businessinsider.com/

“Liquid Biopsy” Chip Detects Metastatic Cancer Cells in a Drop of Blood

A chip developed by mechanical engineers at Worcester Polytechnic Institute (WPI) can trap and identify metastatic cancer cells in a small amount of blood drawn from a cancer patient. The breakthrough technology uses a simple mechanical method that has been shown to be more effective in trapping cancer cells than the microfluidic approach employed in many existing devices.

liquid-biopsy-chip-test

The chip is tested in the lab. The electrodes detect electrical changes that occur when cancer cells are captured (click on the image to enjoy the video)

The WPI device uses antibodies attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells settle to the bottom of the well, where they selectively bind to the antibodies based on their surface markers (unlike other devices, the chip can also trap tiny structures called exosomes produced by cancers cells). This “liquid biopsy,”  could become the basis of a simple lab test that could quickly detect early signs of metastasis and help physicians select treatments targeted at the specific cancer cells identified.

Metastasis is the process by which a cancer can spread from one organ to other parts of the body, typically by entering the bloodstream. Different types of tumors show a preference for specific organs and tissues; circulating breast cancer cells, for example, are likely to take root in bones, lungs, and the brain. The prognosis for metastatic cancer (also called stage IV cancer) is generally poor, so a technique that could detect these circulating tumor cells before they have a chance to form new colonies of tumors at distant sites could greatly increase a patient’s survival odds.

The focus on capturing circulating tumor cells is quite new,” said Balaji Panchapakesan, associate professor of mechanical engineering at WPI and director of the Small Systems Laboratory. “It is a very difficult challenge, not unlike looking for a needle in a haystack. There are billions of red blood cells, tens of thousands of white blood cells, and, perhaps, only a small number of tumor cells floating among them. We’ve shown how those cells can be captured with high precision.

The findings have been described in  the journal Nanotechnology,

Source: https://www.wpi.edu/