Tag Archives: T cells

Biodegradable nanoparticles to program immune cells for cancer treatments

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The Fred Hutchinson Cancer Research Centre in Seattle, Washington has announced a proposed cancer treatment using nanoparticle-programmed T cells according to an April 12, 2017 news release (received via email; also on EurekAlert), Note: A link has been removed,

Researchers at Fred Hutchinson Cancer Research Center have developed biodegradable nanoparticles that can be used to genetically program immune cells to recognize and destroy cancer cells — while the immune cells are still inside the body.

In a proof-of-principle study to be published April 17 [2017] in Nature Nanotechnology, the team showed that nanoparticle-programmed immune cells, known as T cells, can rapidly clear or slow the progression of leukemia in a mouse model.

“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 Fred Hutch’s Dr. Matthias Stephan, the study’s senior author. “The reprogrammed cells begin to work within 24 to 48 hours and continue to produce these receptors for weeks. This suggests that our technology has the potential to allow the immune system to quickly mount a strong enough response to destroy cancerous cells before the disease becomes fatal.”

Cellular immunotherapies have shown promise in clinical trials, but challenges remain to making them more widely available and to being able to deploy them quickly. At present, it typically takes a couple of weeks to prepare these treatments: the T cells must be removed from the patient and genetically engineered and grown in special cell processing facilities before they are infused back into the patient. These new nanoparticles could eliminate the need for such expensive and time consuming steps.

Although his T-cell programming method is still several steps away from the clinic, Stephan imagines a future in which nanoparticles transform cell-based immunotherapies — whether for cancer or infectious disease — into an easily administered, off-the-shelf treatment that’s available anywhere.

“I’ve never had cancer, but if I did get a cancer diagnosis I would want to start treatment right away,” Stephan said. “I want to make cellular immunotherapy a treatment option the day of diagnosis and have it able to be done in an outpatient setting near where people live.”

The body as a genetic engineering lab

Stephan created his T-cell homing nanoparticles as a way to bring the power of cellular cancer immunotherapy to more people.

In his method, the laborious, time-consuming T-cell programming steps all take place within the body, creating a potential army of “serial killers” within days.

As reported in the new study, Stephan and his team developed biodegradable nanoparticles that turned T cells into CAR T cells, a particular type of cellular immunotherapy that has delivered promising results against leukemia in clinical trials.

The researchers designed the nanoparticles to carry genes that encode for chimeric antigen receptors, or CARs, that target and eliminate cancer. They also tagged the nanoparticles with molecules that make them stick like burrs to T cells, which engulf the nanoparticles. The cell’s internal traffic system then directs the nanoparticle to the nucleus, and it dissolves.

The study provides proof-of-principle that the nanoparticles can educate the immune system to target cancer cells. Stephan and his team designed the new CAR genes to integrate into chromosomes housed in the nucleus, making it possible for T cells to begin decoding the new genes and producing CARs within just one or two days.

Once the team determined that their CAR-carrying nanoparticles reprogrammed a noticeable percent of T cells, they tested their efficacy. Using a preclinical mouse model of leukemia, Stephan and his colleagues compared their nanoparticle-programming strategy against chemotherapy followed by an infusion of T cells programmed in the lab to express CARs, which mimics current CAR-T-cell therapy.

The nanoparticle-programmed CAR-T cells held their own against the infused CAR-T cells. Treatment with nanoparticles or infused CAR-T cells improved survival 58 days on average, up from a median survival of about two weeks.

The study was funded by Fred Hutch’s Immunotherapy Initiative, the Leukemia & Lymphoma Society, the Phi Beta Psi Sorority, the National Science Foundation and the National Cancer Institute.

Next steps and other applications

Stephan’s nanoparticles still have to clear several hurdles before they get close to human trials. He’s pursuing new strategies to make the gene-delivery-and-expression system safe in people and working with companies that have the capacity to produce clinical-grade nanoparticles. Additionally, Stephan has turned his sights to treating solid tumors and is collaborating to this end with several research groups at Fred Hutch.

And, he said, immunotherapy may be just the beginning. In theory, nanoparticles could be modified to serve the needs of patients whose immune systems need a boost, but who cannot wait for several months for a conventional vaccine to kick in.

“We hope that this can be used for infectious diseases like hepatitis or HIV,” Stephan said. This method may be a way to “provide patients with receptors they don’t have in their own body,” he explained. “You just need a tiny number of programmed T cells to protect against a virus.”

Here’s a link to and a citation for the paper,

In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers by Tyrel T. Smith, Sirkka B. Stephan, Howell F. Moffett, Laura E. McKnight, Weihang Ji, Diana Reiman, Emmy Bonagofski, Martin E. Wohlfahrt, Smitha P. S. Pillai, & Matthias T. Stephan. Nature Nanotechnology (2017) doi:10.1038/nnano.2017.57 Published online 17 April 2017

This paper is behind a paywall.

Tattoo therapy for chronic disease?

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It’s good to wake up to something truly new. In this case, it’s using tattoos and nanoparticles for medical applications. From a Sept. 22, 2016 news item on ScienceDaily,

A temporary tattoo to help control a chronic disease might someday be possible, according to scientists at Baylor College of Medicine [Texas, US] who tested antioxidant nanoparticles created at Rice University [Texas, US].

A Sept. 22, 2016 Rice University news release, which originated the news item, provides more information and some good explanations of the terms used (Note: Links have been removed),

A proof-of-principle study led by Baylor scientist Christine Beeton published today 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. “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 said.

The soluble nanoparticles synthesized by the Rice lab of chemist James Tour have shown no signs of acute toxicity in prior rodent studies, Huq said. They combine polyethylene glycol with hydrophilic carbon clusters, hence their name, PEG-HCCs. The carbon clusters are 35 nanometers long, 3 nanometers wide and an atom thick, and bulk up to about 100 nanometers in globular form with the addition of PEG. They have proven to be efficient scavengers of reactive oxygen species called superoxide molecules, which are expressed by cells the immune system uses to kill invading microorganisms.

T cells use superoxide in a signaling step to become activated. PEG-HCCs remove this superoxide from the T cells, preventing their activation without killing the cells.

Beeton became aware of PEG-HCCs during a presentation by former Baylor graduate student Taeko Inoue, a co-author of the new study. “As she talked, I was thinking, ‘That has to work in models of multiple sclerosis,’” Beeton said. “I didn’t have a good scientific rationale, but I asked for a small sample of PEG-HCCs to see if they affected immune cells.

“We found they affected the T lymphocytes and not the other splenic immune cells, like the macrophages. It was completely unexpected,” she said.

The Baylor lab’s tests on animal models showed that small amounts of PEG-HCCs injected under the skin are slowly taken up by T lymphocytes, where they collect and inhibit the cell’s function. They also found the nanoparticles did not remain in T cells and dispersed within days after uptake by the cells.

“That’s an issue because you want a drug that’s in the system long enough to be effective, but not so long that, if you have a problem, you can’t remove it,” Beeton said. “PEG-HCCs can be administered for slow release and don’t stay in the system for long. This gives us much better control over the circulating half-life.”

“The more we study the abilities of these nanoparticles, the more surprised we are at how useful they could be for medical applications,” Tour said. The Rice lab has published papers with collaborators at Baylor and elsewhere on using functionalized nanoparticles to deliver cancer drugs to tumors and to quench the overproduction of superoxides after traumatic brain injuries.

Beeton suggested delivering carbon nanoparticles just under the skin rather than into the bloodstream would keep them in the system longer, making them more available for uptake by T cells. And the one drawback – a temporary but visible spot on the skin that looks like a tattoo – could actually be a perk to some.

“We saw it made a black mark when we injected it, and at first we thought that’s going to be a real problem if we ever take it into the clinic,” Beeton said. “But we can work around that. We can inject into an area that’s hidden, or use micropattern needles and shape it.

“I can see doing this for a child who wants a tattoo and could never get her parents to go along,” she said. “This will be a good way to convince them.”

The research was supported by Baylor College of Medicine, the National Multiple Sclerosis Society, National Institutes of Health, the Dan L. Duncan Cancer Center, John S. Dunn Gulf Coast Consortium for Chemical Genomics and the U.S. Army-funded Traumatic Brain Injury Consortium.

That’s an interesting list of funders at the end of the news release.

Here’s a link to and a citation for the paper,

Preferential uptake of antioxidant carbon nanoparticles by T lymphocytes for immunomodulation by Redwan Huq, Errol L. G. Samuel, William K. A. Sikkema, Lizanne G. Nilewski, Thomas Lee, Mark R. Tanner, Fatima S. Khan, Paul C. Porter, Rajeev B. Tajhya, Rutvik S. Patel, Taeko Inoue, Robia G. Pautler, David B. Corry, James M. Tour, & Christine Beeton. Scientific Reports 6, Article number: 33808 (2016) doi:10.1038/srep33808 Published online: 22 September 2016

This paper is open access.

Here’s an image provided by the researchers,

Polyethylene glycol-hydrophilic carbon clusters developed at Rice University were shown to be selectively taken up by T cells, which inhibits their function, in tests at Baylor College of Medicine. The researchers said the nanoparticles could lead to new strategies for controlling autoimmune diseases like multiple sclerosis. (Credit: Errol Samuel/Rice University) - See more at: http://news.rice.edu/2016/09/22/tattoo-therapy-could-ease-chronic-disease/#sthash.sIfs3b0S.dpuf

Polyethylene glycol-hydrophilic carbon clusters developed at Rice University were shown to be selectively taken up by T cells, which inhibits their function, in tests at Baylor College of Medicine. The researchers said the nanoparticles could lead to new strategies for controlling autoimmune diseases like multiple sclerosis. (Credit: Errol Samuel/Rice University)

NANO Magazine’s April 2010 issue country focus: Canada

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I’m a little late to the party but the month isn’t over yet so, today I’m going to focus on Nano Magazine‘s April 2010 issue or more specifically their article about Canada and it’s nanotechnology scene. The magazine (available both in print and online) has selected Canada for its country focus this issue. From the April 2010, issue no. 17 editorial,

The featured country in this issue is Canada, notable for its well funded facilities and research that is aggressively focused on industrial applications. Although having no unifying national nanotechnology initiative, there are many extremely well-funded organisations with world class facilities that are undertaking important nano-related research. Ten of these centres are highlighted, along with a new network that will research into innovative plastics and manufacturing processes, and added value can be gained in this field – with the economic future benefit for Canada firmly in mind!

It’s always an eye-opening experience to see yourself as others see you. I had no idea Canadian research was “aggressively focused on industrial applications.” My view as a Canadian who can only see it from the inside reveals a scattered landscape with a few pockets of concentrated effort. It’s very difficult to obtain a national perspective as communication from the various pockets is occasional, hard to understand and/or interpret at times, and not easily accessible (some of these Canadian nanotechnology groups (in government agencies, research facilities, civil society groups, etc.) seem downright secretive.

As for the ‘aggressive focus on industrial applications’ by Canadians, I found it interesting and an observation I could not have made for two reasons. The first I’ve already noted (difficulty of obtaining the appropriate perspective from the inside) and, secondly, it seems to me that the pursuit of industrial applications is a global obsession and not confined to the field of nanotechnology, as well, I’m not able to establish a basepoint for comparison so the comment was quite a revelation. Still, it should be noted that Nano Magazine itself seems to have a very strong bias towards commercialization and business interests.

The editorial comment about “not have a unifying national nanotechnology initiative” I can heartily second, although the phrase brings the US National Nanotechnology Initiative strongly to mind where I think a plan (any kind of plan) would do just as well.

The article written by Fraser Shand and titled Innovation finds new energy in Western Canada provides a bit of word play that only a Canadian or someone who knows the province of Alberta, which has substantive oil reserves albeit in the sands, would be able to appreciate. Kudos to whoever came up with the title. Very well done!

I have to admit to being a bit puzzled here as I’m not sure if Shand’s article is the sole article about the Canadian nanotechnology scene  (it profiles only the province of Alberta) or if there are other articles profiling pockets of nanotechnology research present, largely in Quebec, Ontario, and British Columbia with smaller pockets in other provinces. I apologize for giving short shrift to six provinces but, as I’ve noted, information is difficult to come by and most of the information I can obtain is from the four provinces mentioned.

From the article,

Steeped in a pioneering spirit and enriched by ingenuity, one of the most exciting, modern day outposts on the nanotechnology frontier is located on the prairies of Western Canada. The province of Alberta is home to some of Canada’s most significant nanotechnology assets and has quickly become a world-destination for nanotechnology research, product development and commercialization.

While Alberta is rooted in the traditional resource sectors of energy, agriculture and forestry, it is dedicated to innovation. The Government of Alberta launched its nanotechnology strategy in 2007, committing $130 million to growth and development over five years. It also created a dedicated team.

Shand goes on to note Canada’s National Institute of Nanotechnology (NINT), located in Edmonton, Alberta’s capital city, and its role in attracting world class researchers (see News Flash below). Other than the brief mention of a federal institution, the focus remains unrelentingly on Alberta and this is surprising since the title misled me into believing that the article would concern itself with Western Canada, which arguably includes the prairie provinces (Manitoba and Saskatchewan) and British Columbia.

Meanwhile, the editorial led me to believe that I would find a national perspective with mention of 10 research centres somewhere in the April 2010 issue. If they are hiding part of the issue, I wish they’d note that somewhere easily visible (front page?) on their website and clarify the situation.

If this is the magazine’s full profile of the Canadian nanotechnology scene, they’ve either come to the conclusion that the only worthwhile work is being done in Alberta (I’m making an inference) or they found the process of gathering information about the other nanotechnology research pockets so onerous that they simply ignored them in favour of pulling a coherent article together.

I have been viewing the site on a regular basis since I heard about the April 2010 issue and this is the only time I’ve seen an article about Canada made available. They seem to have a policy of rotating the articles they make available for free access.

One other thing, a Nanotechnology Asset Map of Alberta is going to be fully accessible sometime in May 2010. I gather some of the folks from the now defunct, Nanotech BC organization advised the folks at nanoAlberta on developing the tool after the successful BC Nanotechnology Asset Map was printed in 2008 (?). I’m pleased to see the Alberta map is online which will make updating a much easier task and it gives a very handy visual representation that is difficult to achieve with print. You can see Alberta’s beta version at nanoAlberta. Scroll down and look to the left of the screen and at the sidebar for a link to the asset map.

I have to give props to the people in the province of Alberta who have supported nanotechnology research and commercialization efforts tirelessly. They enticed the federal government into building NINT in Edmonton by offering to pay a substantive percentage of the costs and have since created several centres for commercialization and additional research as noted in Shand’s article. Bravo!

News Flash: I just (in the last five minutes, i.e., 11:05 am PT) received this notice about the University of Alberta and nanotechnology. From the Eureka Alert notice,

A University of Alberta-led research team has taken a major step forward in understanding how T cells are activated in the course of an immune response by combining nanotechnology and cell biology. T cells are the all important trigger that starts the human body’s response to infection.

Christopher Cairo and his team are studying how one critical trigger for the body’s T cell response is switched on. Cairo looked at the molecule known as CD45 and its function in T cells. The activation of CD45 is part of a chain of events that allows the body to produce T cells that target an infection and, just as importantly, shut down overactive T cells that could lead to damage.

Cairo and crew are working on a national/international team that includes: “mathematician Dan Coombs (University of British Columbia), biochemist Jon Morrow (Yale University Medical School) and biophysicist David Golan (Harvard Medical School).” Their paper is being published in the April issue of the Journal of Biological Chemistry.

Now back to my regular programming: I should also mention Nano Québec which I believe was the first provincial organization founded  in Canada, circa 2005, to support nanotechnology research and commercialization efforts. French language site / English language site

NaNO Ontario has recently organized itself as the Nanotechnology Network of Ontario.

Unfortunately, Nanotech BC no longer exists.

If you know of any other provincial nanotechnology organizations, please do let me know.