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Tools for Alzheimer’s Disease, Cancer Treatment

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LEUVEN, Belgium—Imec, a research center for nanoelectronics and digital technologies based here, is developing tools, modules and nanochips with the goals of advancing cancer treatment, sequencing proteomes and better understanding the brain, Peter Peumans, imec’s CTO for health technologies, told EE Times.

One project focuses on improving the groundbreaking adoptive cell cancer therapy called chimeric antigen receptor (CAR) T-cell therapy, which involves removing a patient’s T-cells, reprogramming those cells so they can recognize and kill a cancerous tumor, multiplying the cells and then injecting the modified cells into the patient’s body to hunt down and eliminate cancer cells, he said. The treatment is effective with an up to 90% remission rate, but it’s also quite expensive: hundreds of thousands of dollars.

The therapy also works well on liquid tumors, such as in leukemia, but not so well on solid tumors, Peumans said. Another challenge is precision—harvesting, sorting and labeling the cells.

“You end up taking billions of cells from the patient and then you’ve got to sort through them, select them and modify them,” he said. “This selection process has a big impact on the ultimate potency and safety of what you’re going to inject. It’s different from any other treatment in the sense that the input material is already quite variable.”

To address these issues, imec has developed modules that can be put together to build systems that can read through these billions of cells at a reasonable pace, identify a large amount of data to determine which cells to keep and then sort those cells into different bins, Peumans said.

“It simplifies the whole process,” he added. “You can do a much better job of cell selection. It gets cheaper, and that’s important for patients. But, more importantly, it also allows you to fine-tune the cell population you’re going to use.”

New research will focus on attacking solid tumors, Peumans said.

Unlike liquid tumors, solid tumors don’t have one clean recognition marker, so the process will require multi-marker recognition strategies. Solid tumors are also better at walling themselves off from the body’s immune system. So next-generation cell therapies will need to be better at recognizing tumor sites and invading those sites, he said.

“It’s more complex engineering, and you’ve got to do a much better job of selecting the cells that are going to be able to do this,” Peumans said. Overall, he added, “We and others in the field think that’s going to ultimately lead to much more powerful therapies.”

Proteome sequencing

Developing tools to sequence proteomes—the entire set of proteins that is or can be expressed by a cell, tissue or organism—is another promising area of work for imec, building on the work of sequencing genomes, he said.

Peter Peumans, imec’s CTO for health technologies
Peter Peumans, imec’s CTO for health technologies (Photo: EE Times)

“An obvious place where deep tech has impacted health is genome sequencing,” he said. Genome sequencing, which has been around for about 20 years, makes it possible to sample blood, look for DNA and identify DNA that might come from a tumor that’s not yet visible.

“The first human genome cost about $100 million to sequence,” Peumans said. “Today, they do it for about $1,000, and it’s still getting cheaper. The proteome is just a lot more complicated because, first of all, there are about 20,000 genes, but there are about a million different proteins. So when you go from gene to protein, you get all kinds of ‘post-translation modifications.’ It gets modified in many different ways. You have a lot more proteins than you have genes.”

Consider that genes and DNA provide the codes that operate your body, Peumans said. But the proteins are the variables: “If you want to debug code, just reading the code doesn’t help a whole lot. You’ve got to actually run it and see what the variables are doing. That’s why it’s important to look at the proteins, because the proteins also perform the function in your body.”

The challenges to map proteomes are the large number of proteins, their dynamic range, the difficulty of copying (as is possible with DNA) and the lack of tools to process any copies, he said.

Success could mean earlier diagnosis of Alzheimer’s disease.

“It’s been 20 years since we’ve been able to do the human genome,” Peumans said. “It’s about time we enable the human proteome, as well, in detail. And it would be game-changing, because today, if you want to understand which protein might be linked to disease, you need a hypothesis first.

“In Alzheimer’s, you’ve got a person with amyloid plaques in the brain,” he continued. “Some of that, some of the proteins of all that process may show up in your bloodstream, in your plasma. But you don’t know which one, so today, you have to make a hypothesis, develop an antibody so you can detect it and then try it out. It’s a very lengthy process. With proteome sequencing, it changes, because you don’t have to make a hypothesis. You say, ‘I’m going to take this cohort of patients. I know some of them will develop Alzheimer’s. I’m going to sequence a proteome and if I see a signal digitally, I can pick it up.’ It’s a much quicker way to make progress.”

Such proteome sequencing is not impossible, Peumans said. “It’s just harder, and that’s why it hasn’t been done yet.”

Understanding the brain

Imec is researching next-generation proteomics, gaining the ability to see what each cell and molecule is doing, he said, with the goal of addressing Alzheimer’s disease. This type of research is an obvious place for imec to work, he said.

“For example, if I take a brain from a deceased Alzheimer’s patient, now I can look at the brain,” he said, to determine what the genome of every cell is doing and what RNA is being produced. “I’d love to see the proteome. That’s not possible” at this point.

“We’re facing an Alzheimer’s tsunami: By 2050, it will be by far the most expensive disease,” Peumans said. “We all get older, of course. It’s devastating because the person in the body disappears. But it’s also very expensive because you need a lot of care. So if you don’t address this, you won’t be able to afford this kind of care anymore. It will be a disaster.”

Physiology and synthetic biology on a chip

Imec is also developing tools to make it possible to put natural and synthetic biology on a chip, he said. This could lead to, for example, a cure for Alzheimer’s disease. Researchers, he noted, have cured millions of mice from Alzheimer’s but not a single human.

“That’s because these animal models are not good predictors of what happens in humans,” Peumans said. “Another problem is [animals] are expensive. Another problem is there are ethical concerns. So we need to come up with a much better way to do this.

“We are invested quite heavily in making it possible to copy human biology in all its complexity,” he added. “The architecture of an organ is not just one single type of cell. It’s quite a complicated architecture. How do we copy that in vitro and how do we then instrument it, the sensors in it and all kinds of things, so we can actually understand what’s going on at a cellular level? So we’re building … the next generation of organ-on-chip approaches that allow you to copy human physiology on a chip.”

Long term, that could mean the ability to copy an individual patient’s biology on a chip and then try out a risky and/or expensive treatment in the lab before treating the patient, Peumans said.

Imec is also researching tools that will enable synthetic biology on a chip, he said. Potential applications include altering yeast or bacteria to produce fuel, decompose plastic or capture CO2, he said.

“But the toolset to engineer biology, to try things out … and see what works best very quickly … doesn’t exist,” Peumans said. “We’re not doing the biology. That’s not our forte. We’re developing the picks and shovels so the gold diggers can do their jobs.”

Filling the skills gap

One challenge that imec faces is a shortage of skilled researchers, Peumans said.

“About 20% of the people we need, we don’t have,” he said. That includes engineers, cell biologists, molecular biologists, chemists, materials scientists and support technicians.

“Training is important,” he said. “But of course, you hire for potential because everything we do is interdisciplinary. You can train an engineer to be conversant in life sciences. Likewise, you can train a biologist to understand an engineering piece. But it’s really hard to find enough talent to do all the projects that we want to do. So today, we’re held back—just by the talent we can source.”

With that shortage in mind, the company has started imec school to train support technicians, he said, adding, “We school people from all different industries to be able to come and work in our lab.”

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