Conquering cancer with implants? Bioengineered vaccines and magnetic nanodiscs show promise

Nov 29, 2009 01:01 PM in Health & Medicine | Post a comment

By Katherine Harmon

Rather than surgically removingtumors, what if doctors could simply implant new tools in our bodies to do the work internally? One team of researchers has been able to vanquish tumors in mice by implanting bioengineered disks filled with tumor-specific antigens, and another has developed magnetized nanodiscs to induce cancer cells destroy themselves.

Numerous cancer vaccines have shown promise in animal models only to later fail to generate results in humans. But an implant-based approach may hold the key, according to a team of immunologists and bioengineers at Harvard University. They designed a tiny polymer disk saturated with dendritic cells and antigens specifically tuned to go after tumor cells. The results, published online November 25 in Science Translational Medicine, show "the power of applying engineering approaches to immunology," David Mooney, a professor of bioengineering ant Harvard's School of Engineering and Applied Sciences, said in a prepared statement.

The principal is the same as a vaccine: prompt the immune system to attack invading cells. However, unlike previously tested injected cancer vaccines, cells from the disk are less prone to die before they can get the job done.

The 8.5-millimeter biodegradable disk can be "inserted anywhere under the skin—much like the implantable contraceptives that can be placed in a woman's arm," Mooney said. "The implants activate an immune response that destroys tumor cells." When the disks were implanted in mice with melanoma, the treatment led to remission and longer lives in "a substantial portion of the population," the authors reported.

Another trick to zapping cancer cells may lie in nano-scale magnets. Previous studies have investigated the use of magnetic fields to kill cancer cells via hyperthermia, but they required a lot more power than the new method and proved to have some dangerous side effects.

A new study, published November 29 in Nature Materials, reports promise in a scaled-down version of this idea to tackle tumors. "Nanomagnetic materials offer exciting avenues for probing cell mechanics and…advancing cancer therapies," the paper authors wrote. Using nanodiscs (about 60 nanometers thick) made of iron and nickel, researchers based in the Argonne National Laboratory in Illinois and the University of Chicago Pritzker School of Medicine have created a so-called "magnetic vortex" in the magnetic alloy with the magnetic charge arranged in concentric circles. "Integration of magnetic materials with biological molecules and therapeutics creates hybrid materials with advanced properties," the authors noted in the paper.

By introducing an alternating magnetic field, researchers made the discs oscillate, thereby damaging the membranes of cancer cells in the lab and causing the cells to die. The researchers needed only a frequency of "a few tens of hertz applied for only 10 minutes" to "achieve cancer-cell destruction in vitro," they wrote. With this approach they rely on neither heat nor mechanical assault, but rather on the oscillation "which triggers the programmed cell-death pathway" via an ionic electrical signal, the authors explained. Thus, "the total energy necessary to accomplish cell death is minute."

While these innovative implant technologies are being tested in the lab, however, cancer continues to be one of the leading causes of death in the U.S. (second only to heart disease), killing more than half a million people last year.

Image of polymer matrix (next to dime for size comparison) courtesy of InCytu, Inc.

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Self-Taught Inventor Creates Homemade Electric Wheelchair

Li Rongbiao, a 67 year old pensioner and inventor, is making headlines in China because of his handmade electric chairs. Also known as the Walking Chair, it is assembled from spare parts and consists of spare wheels that ease stairway access for wheelchairs.

Rongbiao started playing around with the idea of an affordable electric wheelchair when his wife ended up with a broken leg. It so happened that in this period, they faced a number of hassles, including difficulty accessing their fifth floor apartment.

That’s how this self-made inventer found himself buying computer books and looking for financing for his project.

However, the building of the chair took a bit of time since Rongbiao first had to handle all the basics. Thus, he taught himself computer designing for 6 months before spending the rest of the year constructing his dream chair.

As for funding, the innovator was so dedicated to this dream that he pooled all of his income into this project.

This included his savings, pension money as well as odd $70,000 he made from the sale of his apartment.

All this effort is not in vain as his Walking Chair is gaining popularity in China.

In fact, after he demonstrated his invention at one of the biggest disability shows in China, he has been receiving orders for the electric chair. And so, following his visit to this expo, interested parties have bought 30 of his Walking Chairs and there is still a backlog of more than 300 orders.

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Radical new technology could end drilling and filling misery at the dentist

Scientists in Britain have developed a mouthwash that allows plaque-causing bacteria to be destroyed using nothing but a bright light, the light could possibly be attached to the head of a toothbrush.

The researchers say they have been experimenting with standard white light such as a conventional security light.

The new technology works in much the same way as some skin cancer treatments and may be available within three years for use at home.

According to the research team at Leeds Dental Institute a “repair solution” to help the body grow new enamel is also being developed which could do away with the need for “drilling and filling”.

The two projects are led by Professor Jennifer Kirkham, who believes they could make a big difference to dental care.

Professor Kirkham says the mouthwash which uses “photodynamic therapy” could help people who find it hard to use a toothbrush and could also be used to treat gum disease which is a major cause of tooth loss.

Antibacterial molecules in the mouthwash are absorbed only by plaque-causing bacteria, and activated when a bright light is shone into the mouth, killing them.

The technique is similar to that used in certain types of skin cancer, where the substance is painted on the target area, taken up by cancer cells, then exposed to light of a certain wavelength, which activates it to kill the cancer cell.

The researchers say though the molecule is considered to be safe for human consumption, full trials have yet to be completed.

Professor Kirkham says the team are looking for safe new ways to control plaque which do not rely on toothpaste as many who are disabled in some way or another are not able to brush effectively.

Researcher Dr Simon Wood says machines offering photodynamic therapy in dental clinics are already in use, but the aim was to find a way the mouthwash could be used at home.

The “repair solution” which is made from a protein which encourages the laying down of new enamel over microscopic holes in teeth, including those caused by acid produced by plaque bacteria.

The solution is painted on the teeth, it enters the holes and creates a scaffold, it then attracts the calcium needed to patch them.

Professor Kirkham says it could help people with early damage which could eventually lead to dental decay, or those who have tiny holes in their teeth which make consuming hot or cold food or drink painful.

The repair solution will not totally eliminate the need for the dentist’s drill as bigger cavities filled with decay would still have to be treated in the conventional manner.

It is hoped that trials will begin next year and a licence for wider use gained within five years.

November 27th, 2009

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Multiple sclerosis 'blood blockage theory' tested

By Michelle Roberts Health reporter, BBC News The answer may lie with blood flow US scientists are testing a radical new theory that multiple sclerosis (MS) is caused by blockages in the veins that drain the brain. The University of Buffalo team were intrigued by the work of Italian researcher Dr Paolo Zamboni who claims 90% of MS is caused by narrowed veins. He says the restricted drainage, visible on scans, injures the brain leading to MS. He has already widened the blockages in a handful of patients. The US team want to replicate his earlier work before treating patients. Experts welcomed the research saying it was important to confirm the basic science before evaluating any therapy. MS is a long-term inflammatory condition of the central nervous system which affects the transfer of messages from the nervous system to the rest of the body. This is not something patients can expect as a treatment now. This is experimental work and is being tested A spokeswoman for the MS Society The Buffalo team, led by Dr Robert Zivadinov, plan to recruit 1,100 patients with MS and 600 other volunteers as controls who are either healthy or have neurological diseases other than MS. Using Doppler ultrasound, they will scan the patients to see if they can find any blockages within the veins of the neck and brain. If they can prove Dr Zamboni's theory of "chronic cerebrospinal venous insufficiency", they say it will change our understanding of MS. Rewriting science Margaret Paroski, who is chief medical officer at Kaleida Health, where the Buffalo researchers are based, said the work could overturn prevailing wisdom that the damage in MS is predominantly the result of abnormal immune responses. "When I was in medical school, we thought peptic ulcer disease was due to stress. We now know that 80% of cases are due to a bacterial infection. I found the evidence of narrowing - narrowing of the veins just in MS patients Dr Zamboni "Dr Zivadinov's work may lead to a whole different way of thinking about MS." Dr Zamboni, of the University of Ferrara, believes the blockages are the cause rather than the consequence of MS and that they allow iron from the blood to leak into the brain tissue, where it causes damage. He has performed procedures similar to angioplasty to unblock the veins and get the blood flowing normally again. He claims this "liberation procedure" can alleviate many of the symptoms of MS and is due to publish his findings in the Journal of Vascular Surgery. In an interview with CTV News in Canada he said: "I found the evidence of narrowing - narrowing of the veins just in MS patients. "I'm fully convinced that this is very, very important for people." Early days Kevin Lipp, an MS patient from the US, has been symptom-free since being treated by Dr Zamboni. He said: "It's only been 10 months. If nothing happens in the next two to three years, we'll know it's working." The BBC has heard anecdotally of other surgeons in Europe testing out the same treatment. The MS Society said more research was needed to see if this was an avenue that should be explored further. "This is not something patients can expect as a treatment now. This is experimental work and is being tested. We need to know more about its safety and effectiveness." Helen Yates, of the MS Resource Centre, said: "There is no doubt that this area warrants a great deal more study. "This could represent a completely novel approach to MS research which, if proven to be relevant, could be a "sea change" in the understanding of the mechanisms involved in the condition." Source

Tailor-Made HIV/AIDS Treatment Closer to Reality

ScienceDaily (Nov. 26, 2009) — An innovative treatment for HIV patients developed by McGill University Health Centre researchers has passed its first clinical trial with flying colours. The new approach is an immunotherapy customized for each individual patient, and was developed by Dr. J-P. Routy from the Research Institute of the MUHC in collaboration with Dr. R. Sékaly from the Université de Montréal. "This is a vaccine made for the individual patient -- an "haute couture" therapy, instead of an off-the-rack treatment" said Dr Routy.

By "priming" the immune system, as with a vaccine, to fight the specific strain of HIV/AIDS infecting a given patient, the scientists believe they have developed a therapy that shows immense promise and could be an even more effective weapon against the virus than the anti-retroviral cocktails currently in use. The results of the first-stage clinical trials, which tested the therapy in conjunction with anti-retroviral drugs, were published recently in Clinical Immunology. Phase 2 of the clinical trial, which is nearly complete, is testing the therapy's efficacy on its own at 8 different sites in Canada.

The new therapy uses dendritic cells which are removed from each HIV-infected patient and subsequently multiplied in-vitro. Dendritic cells present material from invading viruses on their surface, allowing the rest of the immune system to identify and attack the invaders. "They are the "grand conductors" of the immune response," explains Dr Routy. "With them, you push the immune system, in all its functions, at the same time." In the current trial, dendritic cells were exposed to a sample of HIV RNA (ribonucleic acid) specific to the patient involved. This exposure encouraged the cells to develop defences specific to that viral strain. The modified cells -- called AGS-004 -- were then injected back into the patients.

Not only were there few reported side-effects from the AGS-004, but the researchers also measured increased levels of CD8-lymphocytes in the patients -- the "attack" cells of the human immune system that the treatment is intended to mobilize, thus confirming that the intervention was targeted and controlled.

By boosting the immune system in this way, Routy hopes to develop an HIV/AIDS treatment that will require fewer injections and less long-term toxicity for patients than antriretrovirals.

Dr. Jean-Pierre Routy is a practitioner in the Division of Hematology at the MUHC as well as a researcher in the Infection and Immunity Axis at the Research Institute of the MUHC. He is also an Associate Professor of Hematology at McGill University in addition to a senior clinical researcher with the Fonds de la Recherche en Santé du Québec (FRSQ).

This study was funded by a grant from the Canadian Network for Vaccines and Immunotherapeutics (CANVAC), the Canadian HIV Trials Network (CTN), the National Institutes of Health (NIH) and Argos Therapeutics.

This article was co-authored by Rafick-Pierre Sékaly, Université de Montréal, Mohamed-Rachid Boulassel of the McGill University Health Centre (MUHC), Bader Yassine-Diab and Oleg Yegorov of the Université de Montréal and Centre Hospitalier de l'Université de Montréal (CHUM), Lothar Finke, Don Healey, Renu Jain, Tamara Monesmith ,Charles Nicolette and Irina Tcherepanova of Argos Therapeutics, In, Durham, USA.

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Rectal cancer tumour destroyed by ultrasound

Thursday, 26 November 2009 E-mail this to a friend Printable version

Almost 38.000 patients suffer from rectal cancer per year in the UK A patient with rectal cancer has become the first to have part of their tumour destroyed by ultrasound, say UK doctors. A team of radiologists, surgeons and oncologists at Hammersmith Hospital in London used high intensity ultrasound to heat up and kill the cancer. They say the technique will allow faster and more accurate targeting of tumours than conventional treatments. Hammersmith Hospital will offer the treatment to advanced stage patients. High intensity focused ultrasound (HIFU) is carried out under general anaesthetic. The device can treat tumours up to about 40cc volume and can heat the tissue up to 90 degrees centigrade First patient The first patient to have the procedure has requested anonymity. RECTAL CANCER Almost 38,000 patients suffer from rectal cancer per year in the UK Approximately a third of these cancers are within the rectum Patients often suffer from tenesmus - a painful condition where they find it difficult to empty their bowels and need frequent trips to the toilet They were given a low dose of heat at 70 degrees. Doctors say they are planning to treat 50 more patients and they will closely monitor them to discover the most effective temperature at which to perform the procedure. Unlike radiotherapy, HIFU, can be given to a patient a number of times with minimal risk of toxicity. The study leader, Professor Paul Abel, from Imperial College Healthcare NHS Trust, said: "There is no incision made during the procedure, it's completely non-invasive, so recovery time will be quicker too. "As this is the first time this procedure has ever been performed for rectal cancer, we need to study a wider group of patients to assess how effective the treatment is and whether it has the potential to be curative or to lengthen a patient's life." A spokesman for the charity Beating Bowel Cancer said it welcomes "advances to improve the quality of patients' lives and relieve symptoms". "As this is a world first, we look forward to further studies and results with more patients over a longer period." Source

Turning heat to electricity

David L. Chandler, MIT News Office

MIT research points to a much more efficient way of harvesting electrical power from what would otherwise be wasted heat.

In everything from computer processor chips to car engines to electric powerplants, the need to get rid of excess heat creates a major source of inefficiency. But new research points the way to a technology that might make it possible to harvest much of that wasted heat and turn it into usable electricity.

That kind of waste-energy harvesting might, for example, lead to cellphones with double the talk time, laptop computers that can operate twice as long before needing to be plugged in, or power plants that put out more electricity for a given amount of fuel, says Peter Hagelstein, co-author of a paper on the new concept appearing this month in the Journal of Applied Physics.

Hagelstein, an associate professor of electrical engineering at MIT, says existing solid-state devices to convert heat into electricity are not very efficient. The new research, carried out with graduate student Dennis Wu as part of his doctoral thesis, aimed to find how close realistic technology could come to achieving the theoretical limits for the efficiency of such conversion.

Theory says that such energy conversion can never exceed a specific value called the Carnot Limit, based on a 19th-century formula for determining the maximum efficiency that any device can achieve in converting heat into work. But current commercial thermoelectric devices only achieve about one-tenth of that limit, Hagelstein says. In experiments involving a different new technology, thermal diodes, Hagelstein worked with Yan Kucherov, now a consultant for the Naval Research Laboratory, and coworkers to demonstrate efficiency as high as 40 percent of the Carnot Limit. Moreover, the calculations show that this new kind of system could ultimately reach as much as 90 percent of that ceiling.

Hagelstein, Wu and others started from scratch rather than trying to improve the performance of existing devices. They carried out their analysis using a very simple system in which power was generated by a single quantum-dot device — a type of semiconductor in which the electrons and holes, which carry the electrical charges in the device, are very tightly confined in all three dimensions. By controlling all aspects of the device, they hoped to better understand how to design the ideal thermal-to-electric converter.

Hagelstein says that with present systems it’s possible to efficiently convert heat into electricity, but with very little power. It’s also possible to get plenty of electrical power — what is known as high-throughput power — from a less efficient, and therefore larger and more expensive system. “It’s a tradeoff. You either get high efficiency or high throughput,” says Hagelstein. But the team found that using their new system, it would be possible to get both at once, he says.

A key to the improved throughput was reducing the separation between the hot surface and the conversion device. A recent paper by MIT professor Gang Chen reported on an analysis showing that heat transfer could take place between very closely spaced surfaces at a rate that is orders of magnitude higher than predicted by theory. The new report takes that finding a step further, showing how the heat can not only be transferred, but converted into electricity so that it can be harnessed.

A company called MTPV Corp. (for Micron-gap Thermal Photo-Voltaics), founded by Robert DiMatteo SM ’96, MBA ‘06, is already working on the development of “a new technology closely related to the work described in this paper,” Hagelstein says.

DiMatteo says he hopes eventually to commercialize Hagelstein’s new idea. In the meantime, he says the technology now being developed by his company, which he expects to have on the market next year, could produce a tenfold improvement in throughput power over existing photovoltaic devices, while the further advance described in this new paper could make an additional tenfold or greater improvement possible. The work described in this paper “is potentially a major finding,” he says.

DiMatteo says that worldwide, about 60 percent of all the energy produced by burning fuels or generated in powerplants is wasted, mostly as excess heat, and that this technology could “make it possible to reclaim a significant fraction of that wasted energy.”

When this work began around 2002, Hagelstein says, such devices “clearly could not be built. We started this as purely a theoretical exercise.” But developments since then have brought it much closer to reality.

While it may take a few years for the necessary technology for building affordable quantum-dot devices to reach commercialization, Hagelstein says, “there’s no reason, in principle, you couldn’t get another order of magnitude or more” improvement in throughput power, as well as an improvement in efficiency.

“There’s a gold mine in waste heat, if you could convert it,” he says. The first applications are likely to be in high-value systems such as computer chips, he says, but ultimately it could be useful in a wide variety of applications, including cars, planes and boats. “A lot of heat is generated to go places, and a lot is lost. If you could recover that, your transportation technology is going to work better.”

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United States Patent	7,390,962
Greiff , et al.	June 24, 2008

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Micron gap thermal photovoltaic device and method of making the same

Abstract

A method of making a micron gap thermal photovoltaic device wherein at least one standoff is formed on a photovoltaic substrate, a sacrificial layer is deposited on the photovoltaic substrate and about the standoff, an emitter is attached to the standoff and has a lower planar surface separated from the photovoltaic substrate by the sacrificial layer, and the sacrificial layer is removed to form a sub-micron gap between the photovoltaic substrate and the lower planar surface of the emitter.

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Inventors:	Greiff; Paul (Wayland, MA), DiMatteo; Robert Stephen (Belmont, MA)
Assignee:	The Charles Stark Draper Laboratory, Inc. (Cambridge, MA)
Appl. No.:	10/443,414
Filed:	May 22, 2003

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Liquid battery big enough for the electric grid?

Professor Donald Sadoway’s research in energy storage could help speed the development of renewable energy.

David L. Chandler, MIT News Office

There’s one major drawback to most proposed renewable-energy sources: their variability. The sun doesn’t shine at night, the wind doesn’t always blow, and tides, waves and currents fluctuate. That’s why many researchers have been pursuing ways of storing the power generated by these sources so that it can be used when it’s needed.

So far, those solutions have tended to be too expensive, limited to only certain areas, or difficult to scale up sufficiently to meet the demands. Many researchers are struggling to overcome these limitations, but MIT professor Donald Sadoway has come up with an innovative approach that has garnered significant interest — and some major funding.

The idea is to build an entirely new kind of battery, whose key components would be kept at high temperature so that they would stay entirely in liquid form. The experimental devices currently being tested in Sadoway’s lab work in a way that’s never been attempted in batteries before.

This month, the newly established federal agency ARPA-E (Advanced Research Projects Agency, Energy) announced its first 37 energy-research grants out of a pool of 3,600 applications, and Sadoway’s project to develop utility-scale batteries received one of the largest sums — almost $7 million over five years. And within a few days of the ARPA-E announcement, the French oil company Total — the world’s fifth-largest — announced a $4 million, five-year joint venture with MIT to develop a smaller-scale version of the same technology, suitable for use in individual homes or other buildings.

Because the technology is being patented and could lead to very large-scale commercialization, Sadoway will not discuss the details of the materials being used. But both Sadoway and ARPA-E say the battery is based on low-cost, domestically available liquid metals that have the potential to shatter the cost barrier to large-scale energy storage as part of the nation's energy grid. In announcing its funding of Sadoway’s work, ARPA-E said the battery technology “could revolutionize the way electricity is used and produced on the grid, enabling round-the-clock power from America's wind and solar power resources, increasing the stability of the grid, and making blackouts a thing of the past.”

Andrew Chung, a principal at Lightspeed Venture Partners in Menlo Park, Calif., which has no equity stake in Sadoway’s project at this point, says that “grid-scale storage is an area that’s set to explode in the next decade or so,” and is one that his company is following closely. The liquid battery concept Sadoway is developing “is an exciting approach to solving the problem,” he says.

Big is beautiful

Most battery research, Sadoway says, has been aimed at improving storage for portable or mobile systems such as cellphones, computers and cars. The requirements for such systems, including very low weight and high safety, are very different from the needs of a grid-scale, fixed-location battery system. “What I did was completely ignore the conventional technology used for portable power,” he says. The different set of requirements for stationary systems “opens up a whole new range of possibilities.”

A large, utility-owned system “doesn’t have to be crash-worthy; it doesn’t have to be ‘idiot-proof’ because it won’t be in the hands of the consumer.” And while consumers are willing to pay high prices, pound-for-pound, for the small batteries used in high-value portable devices, the biggest constraint on utility-sized systems is cost. In order to compete with present fossil-fuel power systems, he says, “it has got to be cheap to build, cheap to maintain, last a long time with minimal maintenance, and store enormous amounts of energy.”

And so the new liquid batteries that Sadoway and his team, including graduate student David Bradwell, are designing use low-cost, abundant materials. The basic principle is to place three layers of liquid inside a container: Two different metal alloys, and one layer of a salt. The three materials are chosen so that they have different densities that allow them to separate naturally into three distinct layers, with the salt in the middle separating the two metal layers —like novelty drinks with different layers.

The energy is stored in the liquid metals that want to react with one another but can do so only by transferring ions — electrically charged atoms of one of the metals — across the electrolyte, which results in the flow of electric current out of the battery. When the battery is being charged, some ions migrate through the insulating salt layer to collect at one of the terminals. Then, when the power is being drained from the battery, those ions migrate back through the salt and collect at the opposite terminal.

The whole device is kept at a high temperature, around 700 degrees Celsius, so that the layers remain molten. In the small devices being tested in the lab, maintaining this temperature requires an outside heater, but Sadoway says that in the full-scale version, the electrical current being pumped into, or out of, the battery will be sufficient to maintain that temperature without any outside heat source.

While some previous battery technologies have used one liquid-metal component, this is the first design for an all-liquid battery system, Sadoway says. “Solid components in batteries are speed bumps. When you want ultra-high current, you don’t want any solids.”

Inspiration from aluminum

The initial inspiration for the idea came from thinking about a very different technology, Sadoway says: one of the biggest users of electrical energy, aluminum smelting plants. Sadoway realized that this was one of the few existing examples of a system that could sustain extremely high levels of electrical current over a sustained period of years at a time. “It’s an electrochemical process that runs at high temperatures, and at a current of hundreds of thousands of amps,” he says. In a sense, the new concept is like an aluminum plant running in reverse, producing power instead of consuming it.

Chung says that from the point of view of a venture capitalist, the research is particularly intriguing for several reasons. Not only does it offer the potential to significantly lower the cost and increase cycle life [the number of times it can be charged and discharged] of large-scale electricity storage, but it also suggests that the risk typically associated with an early stage research project may be lower because the system draws on decades of experience in the design and operation of aluminum production facilities. “That gives us added confidence that some of the targets around cost, scalability and safety have merit,” he says.

The team is now testing a number of different variations of the exact composition of the materials in the three layers, and of the design of the overall device. Sadoway says that thanks to initial funding through the Deshpande Center and the Chesonis Family Foundation, he and his team were able to develop the concept to the point of demonstrating a proof-of-principle at the laboratory scale. That, in turn, made it possible to get the large grants to develop the technology further.

“It’s an example of work that sprang from basic science, was developed to a pilot scale, and now is being scaled up to have a real transformational impact in the world,” says Ernest Moniz, director of the MIT Energy Initiative.

The laboratory tests have provided “some measure of confidence,” Sadoway says. But many more tests will be needed to “demonstrate that the idea is scalable to industrial size, at competitive cost.” But while he is very confident that it will all work, there are a lot of unknowns, he says, including how to design and build the necessary containers, electrical control systems, and connections.

“We’re talking about batteries of a size never seen before,” he says. And the system they develop has to include everything, including control systems and charger electronics on an unprecedented scale.

For Sadoway, the project is worth pursuing despite its daunting challenges, because the potential impact is so great. “I’m not doing this because I want another journal publication,” Sadoway says. “It’s about making a difference … It’s an opportunity to invent our way out of the energy problem.”

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