Israeli Scientists Claim They’re On The Path To A Cure For Cancer – ACS Cautions


Israele 3

It doesn’t seem possible. But they say it’s true. A small team of Israeli scientists is telling the world they will have the first “complete cure” for cancer within a year, The Jerusalem Post reported on Monday. And not only that, but they claim it will be brief, cheap and effective and will have no or minimal side-effects.

“We believe we will offer in a year’s time a complete cure for cancer,” said Dan Aridor, chairman of the board of Accelerated Evolution Biotechnologies Ltd. (AEBi), a company founded in 2000 in the ITEK incubator in the Kiryat Weizmann Science Park in Ness Ziona, Israel, just north of the Weizmann Institute of Science in Rehovot, Israel.

A development-stage biopharmaceutical company engaged in discovery and development of therapeutic peptides, AEBi developed the SoAP platform, a combinatorial biology screening platform technology, which provides functional leads—agonist, antagonist, inhibitor, etc.—to very difficult targets.

Still skepticism was high among those in the know. Weighing in on behalf of the American Cancer Society (ACS) on his blog, “A Cure For Cancer? Not So Fast,” Len Lichtenfeld, MD, ACS chief medical officer cautioned: “…it goes without saying, we all share the aspirational hope that they are correct. Unfortunately, we must be aware that this is far from proven as an effective treatment for people with cancer, let alone a cure.”

YOUNG ISRAELI CANCER RESEARCHRead More: Why Others Think This Claim Is Not Likely to Happen

Lichtenfeld went on to list several key points that he says must be kept in mind no matter what media reports say:

1. This is a news report based on limited information provided by researchers and a company working on this technology. It apparently has not been published in the scientific literature where it would be subject to review, support and/or criticism from knowledgeable peers.

2. My colleagues here at American Cancer Society tell me phage or peptide display techniques, while very powerful research tools for selecting high affinity binders, have had a difficult road as potential drugs. If this group is just beginning clinical trials, they may well have some difficult experiments ahead.

3. This is based on a mouse experiment which is described as “exploratory.” It appears at this point there is not a well-established program of experiments which could better define how this works—and may not work—as it moves from the laboratory bench to the clinic.

4. We all have hope that a cure for cancer can be found and found quickly. It is certainly possible this approach may be work. However, as experience has taught us so many times, the gap from a successful mouse experiment to effective, beneficial application of exciting laboratory concepts to helping cancer patients at the bedside is in fact a long and treacherous journey, filled with unforeseen and unanticipated obstacles.

5. It will likely take some time to prove the benefit of this new approach to the treatment of cancer. And unfortunately–based on other similar claims of breakthrough technologies for the treatment of cancer–the odds are that it won’t be successful.

“Our hopes are always on the side of new breakthroughs in the diagnosis and treatment of cancer. We are living in an era where many exciting advances are impacting the care of patients with cancer,” Lichtenfeld went on. “We hope that this approach also bears fruit and is successful. At the same time, we must always offer a note of caution that the process to get this treatment from mouse to man is not always a simple and uncomplicated journey.”

From Forbes – Robin Seaton Jefferson – 

Advertisements

‘Swiss army knife’ Nanovaccine carries multiple weapons to battle tumors – cancer


Swiss Army Knife of Nano Ps 171129163851_1_540x360
Source: National Institute of Biomedical Imaging and Bioengineering
Summary: Researchers have developed a synergistic cancer nanovaccine packing DNA and RNA sequences that modulate the immune response, along with anti-tumor antigens, into one small nanoparticle.
(Above) Large particles (left) containing the DNA and RNA components are coated with electronically charged molecules that shrink the particle. The tumor-specific neoantigen is then complexed with the surface to complete construction of the nanovaccine. Upper left: electron micrograph of large particle. Credit: Zhu, et al. Nat Comm.

 

 

Scientists are using their increasing knowledge of the complex interaction between cancer and the immune system to engineer increasingly potent anti-cancer vaccines. The nanovaccine produced an immune response that specifically killed tumor tissue, while simultaneously inhibiting tumor-induced immune suppression to block lung tumor growth in a mouse model of metastatic colon cancer.

Now researchers at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have developed a synergistic nanovaccine packing DNA and RNA sequences that modulate the immune response, along with anti-tumor antigens, into one small nanoparticle. The nanovaccine produced an immune response that specifically killed tumor tissue, while simultaneously inhibiting tumor-induced immune suppression. Together this blocked lung tumor growth in a mouse model of metastatic colon cancer.

The molecular dance between cancer and the immune system is a complex one and scientists continue to identify the specific molecular pathways that rev up or tamp down the immune system. Biomedical engineers are using this knowledge to create nanoparticles that can carry different molecular agents that target these pathways. The goal is to simultaneously stimulate the immune system to specifically attack the tumor while also inhibiting the suppression of the immune system, which often occurs in cancer patients. The aim is to press on the gas pedal of the immune system while also releasing the emergency brake.

A key hurdle is to design a system to reproducibly and efficiently create a nanoparticle loaded with multiple agents that synergize to mount an enhanced immune attack on the tumor. Engineers at the NIBIB report the development and testing of such a nanovaccine in the November issue of Nature Communications.

Making all the parts fit

Guizhi Zhu, Ph.D., a post-doctoral fellow in the NIBIB Laboratory of Molecular Imaging and Nanomedicine (LOMIN) and lead author on the study, explains the challenge. “We are very excited about putting multiple cooperating molecules that have anti-cancer activity into one nanovaccine to increase effectiveness. However, the bioengineering challenge is fitting everything in to a small particle and designing a way to maintain its structural integrity and biological activity.”

Zhu and his colleagues have created what they call a “self-assembling, intertwining DNA-RNA nanocapsule loaded with tumor neoantigens.” They describe it as a synergistic vaccine because the components work together to stimulate and enhance an immune attack against a tumor.

The DNA component of the vaccine is known to stimulate immune cells to work with partner immune cells for antitumor activation. The tumor neoantigens are pieces of proteins that are only present in the tumor; so, when the DNA attracts the immune cells, the immune cells interact with the tumor neoantigens and mount an expanded and specific immune response against the tumor. The RNA is the component that inhibits suppression of the immune system. The engineered RNA binds to and degrades the tumor’s mRNA that makes a protein called STAT3. Thus, the bound mRNA is blocked from making STAT3, which may suppress the immune system. The result is an enhanced immune response that is specific to the tumor and does not harm healthy tissues.

In addition to engineering a system where the DNA, RNA and tumor neoantigens self-assemble into a stable nanoparticle, an important final step in the process is shrinking the particle. Zhu explains: “Shrinking the particle is a critical step for activating an immune response. This is because a very small nanoparticle can more readily move through the lymphatic vessels to reach the parts of the immune system such as lymph nodes. A process that is essential for immune activation.”

The method for shrinking also had to be engineered. This was achieved by coating the particle with a positively charged polypeptide that interacts with the negatively charged DNA and RNA components to condense it to one-tenth of its original size.

Testing the nanovaccine

To create a model of metastatic colon cancer, the researchers injected human colon cancer cells into the circulation of mice. The cells infiltrate different organs and grow as metastatic colon cancer. One of the prime sites of metastasis is the lung.

The nanovaccine was injected under the skin of the mice 10, 16, and 22 days after the colon cancer cells were injected. To compare to the nanovaccine, two control groups of mice were analyzed; one group was injected with just the DNA and the neoantigen in solution but not formed into a nanovaccine particle, and the second control group was injected with an inert buffer solution.

At 40 days into the experiment, lung tumors from the nanovaccine-treated and the control groups were assessed by PET-CT imaging, and then removed and weighed. In mice treated with the nanovaccine, tumors were consistently one tenth the size of the tumors that were found in mice in both control groups.

Further testing revealed that mice receiving the nanovaccine had a significant increase in circulating cytotoxic T lymphocytes (CTLs) that specifically targeted the neoantigen on the colon cancer cells. CTLs are cells that attack and kill virus-infected cells and those damaged in other ways, such as cancerous cells.

An important aspect of the nanovaccine approach is that it mounts an anti-tumor immune response that circulates through the system, and therefore is particularly valuable for finding and inhibiting metastatic tumors growing throughout the body.

The researchers view their nanovaccine as an important part of eventual therapies combining immunotherapy with other cancer killing approaches.

Story Source:

Materials provided by National Institute of Biomedical Imaging and BioengineeringNote: Content may be edited for style and length.


Journal Reference:

  1. Guizhi Zhu, Lei Mei, Harshad D. Vishwasrao, Orit Jacobson, Zhantong Wang, Yijing Liu, Bryant C. Yung, Xiao Fu, Albert Jin, Gang Niu, Qin Wang, Fuwu Zhang, Hari Shroff, Xiaoyuan Chen. Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapyNature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-01386-7

Rice University: Antioxidant compounds mimic effective graphene agents, show potential for therapies 


PEG-PDI, which incorporates a compound long used as a red dye, changes to greenish-blue with the addition of potassium superoxide as it converts the superoxide to dioxygen. Adding more further quenches the reactive oxygen species superoxide, turning the solution purple. Adding hydrogen peroxide in the last step clarifies the liquid, showing that a build-up of excess hydrogen peroxide can deactivate the structure. PEG-PDI, created at Rice University, shows potential as a biological antioxidant. Credit: Tour Group/Rice University

Treated particles of graphene derived from carbon nanotubes have demonstrated remarkable potential as life-saving antioxidants, but as small as they are, something even smaller had to be created to figure out why they work so well.

 

Researchers at Rice University, the McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine created single-molecule compounds that also quench damaging reactive oxygen species (ROS) but are far easier to analyze using standard scientific tools. The molecules may become the basis for new antioxidant therapies in their own right.

The research appears in the American Chemical Society journal ACS Nano.

The original compounds are hydrophilic carbon clusters functionalized with polyethylene glycol, known as PEG-HCCs and created by Rice and Baylor scientists five years ago. The particles help neutralize ROS molecules overexpressed by the body’s cells in response to an injury before they damage cells or cause mutations.

PEG-HCCs show promise for treating cancer, rebooting blood flow in the brain after traumatic injury and controlling chronic diseases.

The new particles, called PEG-PDI, consist of polyethylene glycol and perylene diimide, a compound used as a dye, the color in red car paint and in solar cells for its light-absorbing properties. Their ability to accept electrons from other molecules makes them functionally similar to PEG-HCCs.

They’re close enough to serve as an analog for experiments, according to Rice chemist James Tour, who led the study with University of Texas biochemist Ah-Lim Tsai.

The researchers wrote that the molecule is not only the first example of a small molecular analogue of PEG-HCCs, but also represents the first successful isolation of a PDI radical anion as a single crystal, which allows its structure to be captured with X-ray crystallography.

“This allows us to see the structure of these active particles,” Tour said. “We can get a view of every atom and the distances between them, and get a lot of information about how these molecules quench destructive oxidants in biological tissue.

“Lots of people get crystal structures for stable compounds, but this is a transient intermediate during a catalytic reaction,” he said. “To be able to crystallize a reactive intermediate like that is amazing.”

Antioxidant compounds mimic effective graphene agents, show potential for therapies 





The crystal structure of PEG-PDI is achieved using cobaltocene as a reducing agent and omitting solvents and hydrogen atoms for clarity. Carbon atoms are gray, nitrogens are blue, oxygens red and cobalts purple. The molecules created by scientists at Rice University, the McGovern Medical School at the University of Texas Health Science Center at Houston and Baylor College of Medicine are efficient antioxidants and help scientists understand how larger nanoparticles quench damaging reactive oxygen species in the body. Credit: Tour Group

PEG-HCCs are about 3 nanometers wide and 30 to 40 nanometers long. By comparison, much simpler PEG-PDI molecules are less than a nanometer in width and length.

 

PEG-PDI molecules are true mimics of superoxide dismutase enzymes, protective antioxidants that break down toxic superoxide radicals into harmless molecular oxygen and hydrogen peroxide. The molecules pull electrons from unstable ROS and catalyze their transformation into less-reactive species.

Testing the PEG-PDI molecules can be as simple as putting them in a solution that contains reactive oxygen species molecules like potassium superoxide and watching the solution change color. Further characterization with electron paramagnetic resonance spectroscopy was more complicated, but the fact that it’s even possible makes them powerful tools in resolving mechanistic details, the researchers said.

Tour said adding polyethylene glycol makes the molecules soluble and also increases the amount of time they remain in the bloodstream. “Without PEG, they just go right out of the system through the kidneys,” he said.

When the PEG groups are added, the molecules circulate longer and continue to catalyze reactions.

He said PEG-PDI is just as effective as PEG-HCCs if measured by weight. “Because they have so much more surface area, PEG-HCC particles probably catalyze more parallel reactions per particle,” Tour said. “But if you compare them with PEG-PDI by weight, they are quite similar in total catalytic activity.”

Understanding the structure of PEG-PDI should allow researchers to customize the molecule for applications. “We should have a tremendous ability to modify the molecule’s structure,” he said. “We can add anything we want, exactly where we want, for specific therapies.”

The researchers said PEG-PDI may also be efficient metal- and protein-free catalysts for oxygen reduction reactions used in industry and essential to fuel cells. They are intrinsically more stable than enzymes and can function in much a wider pH range, Tsai said.

Co-author Thomas Kent, a professor of neurology at Baylor who has worked on the project from the start, noted small molecules have a better chance to get on the fast track to approval for therapy by the Food and Drug Administration than nanotube-based agents.
“A small molecule that is not derived from larger nanomaterial may have a better chance of approval to use in humans, assuming it is safe and effective,” he said.

Tour said PEG-PDI serves as a precise model for other graphene derivatives like graphene oxide and permits a more detailed study of graphene-based nanomaterials.

“Making nanomaterials smaller, from well-defined molecules, permits 150 years of synthetic chemistry methods to address the mechanistic questions within nanotechnology,” he said.

 

More information: Almaz S. Jalilov et al. Perylene Diimide as a Precise Graphene-Like Superoxide Dismutase Mimetic, ACS Nano (2017). DOI: 10.1021/acsnano.6b08211

Provided by: Rice University

MIT: Seeking sustainable solutions through Nanotechnology – Engineer’s designs may help purify water, diagnose disease in remote regions of world.


mit-karnik-rohit-1“I try to guide my research by … asking myself the question, ‘What can we do today that will have a lasting impact and be conducive to a sustainable human civilization?’” says Rohit Karnik, an associate professor in MIT’s Department of Mechanical Engineering. Photo: Ken Richardson

In Rohit Karnik’s lab, researchers are searching for tiny solutions to some of the world’s biggest challenges.

In one of his many projects, Karnik, an associate professor in MIT’s Department of Mechanical Engineering, is developing a new microfluidic technology that can quickly and simply sorts cells from small samples of blood. The surface of a microfluidic channel is patterned to direct certain cells to roll toward a reservoir for further analysis, while allowing the rest of the blood sample to pass through. With this design, Karnik envisions developing portable, disposable devices that doctors may use, even in remote regions of the world, to quickly diagnose conditions ranging from malaria to sepsis.

Karnik’s group is also tackling issues of water purification. The researchers are designing filters from single layers of graphene, which are atom-thin sheets of carbon known for their exceptional strength. Karnik has devised a way to control the size and concentration of pores in graphene, and is tailoring single layers to filter out miniscule and otherwise evasive contaminants. The group has also successfully filtered salts using the technique and hopes to develop efficient graphene filters for water purification and other applications. Silver Nano P clean-drinking-water-india

In looking for water-purifying solutions, Karnik’s group also identified a surprisingly low-tech option: the simple tree branch. Karnik found that the pores within a pine branch that normally help to transport water up the plant are ideal for filtering bacteria from water. The group has shown that a peeled pine branch can filter out up to 99.00 percent of E. coli from contaminated water. Karnik’s group is building up on this work to explore the potential for simple and affordable wood-based water purification systems.

“I try to guide my research by long-term sustainability, in a specific sense, by asking myself the question, ‘What can we do today that will have a lasting impact and be conducive to a sustainable human civilization?’ Karnik says. “I try to align myself with that goal.”

From stargazer to tinkerer

Karnik was born and raised in Pune, India, which was then a relatively quiet city 100 miles east of Mumbai. Karnik describes himself while growing up as shy, yet curious about the way the world worked. He would often set up simple experiments in his backyard, seeing, for instance, how transplanting ants from one colony to another would change the ants’ behavior. (The short answer: They fought, sometimes to the death.) He developed an interest in astronomy early on and often explored the night sky with a small telescope, from the roof of his family’s home.

“I used to take my telescope up to the terrace in the middle of the night, which required three different trips up six or seven flights of stairs,” Karnik says. “I’d set the alarm for 3 a.m., go up, and do quite a bit of stargazing.”

That telescope would soon serve another use, as Karnik eventually found that, by inverting it and adding another lens, he could repurpose the telescope as a microscope.

“I built a little setup so I could look at different things, and I used to collect stuff from around the house, like onion peels or fungus growing on trees, to look at their cells,” Karnik says.

When it came time to decide on a path of study, Karnik was inspired by his uncle, a mechanical engineer who built custom machines “that did all kinds of things, from making concrete bricks, to winding up springs,” Karnik says. “What I saw in mechanical engineering was the ability to building something that integrates across different disciplines.”

Seeking balance and insight

As an entering student at the Indian Institute of Technology Bombay, Karnik chose to study mechanical engineering over electrical engineering, which was the more popular choice among students at the time. For his thesis, he looked for new ways to model three-dimensional cracks in materials such as steel beams.

Casting around for a direction after graduating, Karnik landed on the fast-growing field of nanotechnology. Arun Majumdar, an IIT alum and professor at the University of California at Berkeley, was studying energy conversion and biosensing in nanoscale systems. Karnik joined the professor’s lab as a graduate student, moving to California in 2002. For his graduate work, Karnik helped to develop a microfluidic platform to rapidly mix the contents of and test reactions occurring within droplets. He followed this work up with a PhD thesis in which he explored how fluid, flowing through tiny, nanometer-sized channels, can be controlled  to sense and direct ions and molecules.

Toward the end of his graduate work, Karnik interviewed for and ultimately accepted a faculty position at MIT. However, he was still completing his PhD thesis at Berkeley and had less than 4 years of experience beyond his bachelor’s degree. To help ease the transition, MIT offered Karnik an interim postdoc position in the lab of Robert Langer, the David H. Koch Institute Professor and a member of the Koch Institute for Integrative Cancer Research.

“It was an insightful experience,” Karnik remembers. “For a mechanical engineer who’s never been outside mechanical engineering, I basically had little experience how to do things in biology. It opened up possibilities for working with the biomedical community.”

When Karnik finally assumed his position as assistant professor of mechanical engineering in 2007, he experienced a tidal wave of deadlines, demands, and responsibilities — a common initiation for first-time faculty.

“By its nature the job is overwhelming,” Karnik says. “The trick is how to maintain balance and sanity and do the things you like, without being distracted by the busyness around you, in some sense.”

He says several things have helped him to handle and even do away with stress: walks, which he takes each day to work and around campus, as well as yoga and meditation.

“If you can see things the way they are, by clearing away the filters your mind puts in place, you can get a clear perspective, and there are a lot of insights that come through,” Karnik says.

Nanoparticle reduces targeted cancer drug’s toxicity


Cancer Nanoparticle Targets 160210165715_1_540x360In one of the first efforts to date to apply nanotechnology to targeted cancer therapeutics, researchers have created a nanoparticle formulation of a cancer drug that is both effective and nontoxic — qualities harder to achieve with the free drug. Their nanoparticle creation releases the potent but toxic targeted cancer drug directly to tumors, while sparing healthy tissue.

The findings in rodents with human tumors have helped launch clinical trials of the nanoparticle-encapsulated version of the drug, which are currently underway. Aurora kinase inhibitors are molecularly targeted agents that disrupt cancer’s cell cycle.

While effective, the inhibitors have proven highly toxic to patients and have stalled in late-stage trials. Development of several other targeted cancer drugs has been abandoned because of unacceptable toxicity. To improve drug safety and efficacy, Susan Ashton and colleagues designed polymeric nanoparticles called Accurins to deliver an Aurora kinase B inhibitor currently in clinical trials.

The nanoparticle formulation used ion pairing to efficiently encapsulate and control the release of the drug. In colorectal tumor-bearing rats and mice with diffuse large B cell lymphoma, the nanoparticles accumulated specifically in tumors, where they slowly released the drug to cancer cells. Compared to the free drug, the nanoparticle-encapsulated inhibitor blocked tumor growth more effectively at one half the drug dose and caused fewer side effects in the rodents.

Cancer Nanoparticle Targets 160210165715_1_540x360

The polymeric nanoparticle Accurin encapsulates the clinical candidate AZD2811, an Aurora B kinase inhibitor. This material relates to a paper that appeared in the Feb. 10, 2016 issue of Science Translational Medicine, published by AAAS. The paper, by S. Ashton at institution in location, and colleagues was titled, “Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo.”
Credit: Ashton et al., Science Translational Medicine (2016)

A related Focus by David Bearss offers more insights on how Accurin nanoparticles may help enhance the safety and antitumor activity of Aurora kinase inhibitors and other molecularly targeted drugs.


Story Source:

The above post is reprinted from materials provided by American Association for the Advancement of Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Susan Ashton, Young Ho Song, Jim Nolan, Elaine Cadogan, Jim Murray, Rajesh Odedra, John Foster, Peter A. Hall, Susan Low, Paula Taylor, Rebecca Ellston, Urszula M. Polanska, Joanne Wilson, Colin Howes, Aaron Smith, Richard J. A. Goodwin, John G. Swales, Nicole Strittmatter, Zoltán Takáts, Anna Nilsson, Per Andren, Dawn Trueman, Mike Walker, Corinne L. Reimer, Greg Troiano, Donald Parsons, David De Witt, Marianne Ashford, Jeff Hrkach, Stephen Zale, Philip J. Jewsbury, and Simon T. Barry. Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Science Translational Medicine, 2016 DOI: 10.1126/scitranslmed.aad2355