MIT

by

Running the Engine for your own cells

MIT’s tough-tech accelerator joins the march toward truly individual therapies.

Sometimes, limitations on a given technology that seem set in stone instead will vanish pretty quickly. That might be happening in the field of cell therapies, where treatments that remove, turbocharge and reinfuse your own cells might seem way too difficult and expensive for all but the deadliest diseases.

But maybe not.

That’s what experts keep telling me as I work on a Nature story about regulatory T cell therapies for autoimmune diseases. Maybe the bring-your-own-cells approach will work out for a number of these conditions, and maybe even we’ll see that in clinics this decade.

If so, these living drugs will be built on progress in immunology, cell engineering for chimeric antigen receptor (CAR) T cell treatments for blood cancers, stem cell research, and genome editing tools headlined by CRISPR-Cas9. And the drugmakers will employ industrial tools provided by startup firms.

Two examples of such infrastructure platforms come from MIT’s Engine, a “tough-tech” accelerator for startup firms that attack global societal problems.

The Engine has placed very few bets on biomedical firms, but Cellino Biotech and Kytopen are exceptions.

Cellino “has the potential to manufacture personalized cell therapies at-scale for the first time,” as co-founder and CEO Nabiha Saklayen puts it. “Progressing towards scalable stem cell manufacturing is the only way to provide personalized cell therapies to all patients.”

“Kytopen aims to transform the cell and gene therapy industry with its microfluidics and electric-field-based platform that can automate and manufacture the genetic engineering of cells 10,000x times faster than current methods,” the company says.

In autoimmune labs and clinics, hopes are high for individualized cell therapies. “In the right context, these cells can be effective in resetting the immune system,” one prominent immunologist told me. “This can be really transformational.”

Image courtesy Doug Melton’s lab at Harvard, now routinely churning out batches of half a billion human cells that act very much like the pancreatic islet cells that fail in type 1 diabetes.

by

An Engine for solving societal problems

MIT’s accelerator brings an incubator and funding to startups that matter.

the_engine_logo

“One of my frustrations as an academic is that over the last twelve years we’ve produced a lot of really useful methods and techniques, and almost none of them has been put into practice,” one prominent MIT professor told me earlier this year. “This is not an unusual problem for academics. But it’s frustrating to have things that you know could help and they’re not helping.”

Generating the intellectual property (IP) is only the very first step on the road to the real world. Established companies often are not very interested in IP, even game-changing IP. They are more likely to want prototypes, and people who know how to build the prototypes.

They want, in brief, to work with startups.

That’s one reason why this professor launched a startup. It’s also one reason why MIT actively spreads the entrepreneurial gospel to students and staff who might not have considered it a few years back, and keeps deepening its “environmental ecosystem” of competitions and advisory networks and resources like the Startup Exchange.

And it’s the thinking behind the Engine, the startup accelerator that MIT president L. Rafael Reif announced yesterday. The Engine will combine an incubator with funding for startups focused on real needs.

“When it comes to the most important problems humanity needs to solve — climate change, clean energy, fresh water and food for the world, cancer, and infectious disease, to name a few — there is no app for that,” as Reif explained in the Boston Globe. “We believe the Engine will help deliver important answers for addressing such intractable problems — answers that might otherwise never leave the lab.”

Venture capitalists do a reasonable job of funding many tech companies, but very few VCs are interested in startups that may take more than five years to pay off. The Engine won’t sponsor quick-turnaround firms, or companies that join the thundering herds of marketing middlemen, or oddities like the outfit that claims to deliver wine matched to your DNA.

Instead the funds might go to biotechs, like Oxalys, which do very well if they can even get their drug candidates into first clinical trials within a few years. Or makers of industrial products, like Dropwise’s energy-saving coatings for power plants, which manufacturers probably will adopt quite slowly because that’s how that industry works. Or any number of truly innovative, truly needed products and services.

It will take a decade or more to see how the Engine’s bets turn out. Many will fail. But these are bets we need.

by

The write stuffing

Backlit_keyboard

When I graduated from high school, all I really knew professionally was that I wanted to write on many topics. Last weekend when people at my high school reunion asked politely what I wrote about, I did find myself saying, many topics—in fact, way more now than when I worked as a staff journalist. Okay, I’m not covering the full human condition. Much of the universe is unexplored. But so far this year I’ve done stories about medical hackathons and crowdsourced scientific challenges, global data security and global financial crises (still separate topics so far!), drug development crises, the future of suburbia, steam power, gene therapy,  agricultural particulates, the challenges of small data in healthcare, chemical sensing on a chip, employee cross-training,  urban carbon dioxide release, jet engines, zebrafish brains, surgery by telemedicine and robotics manufacturing, among others.

by

Capping off

sphere_scarringAn MIT alginate microcapsule holding islet cells (in green) and being covered by immune cells (in blue and magenta). Image credit: Omid Veiseh, Joshua Doloff, Minglin Ma and Arturo Vegas.

There’s a worldwide deficit in insulin-producing beta cells, for people with either type 1 or type 2 diabetes, Harvard’s Doug Melton told a session at the ADA annual scientific conference on Friday.

“It’s a completely non-trivial thing that you can now make billions of human beta cells,” he said. “We spent more than a decade trying to march these cells through this procedure.”

Currently, it takes his lab about 40 days to produce the cells at a cost of about $6,000 per flask, but Melton is confident that these numbers can be chopped down.

The achievement required not only brilliant scientific detective legwork, especially on the last steps of differentiation, but lab drudgework on a dramatic scale.

Picking apart the steps that drive cells into beta shape, “we had to sort out three or four factors at a time,” he noted. The lab ran screens of small molecules to find what combinations were effective. Testing eight small molecules, in three concentrations, for different periods, in triplicate meant about 65,000 combinations to examine per screen.

The lab of MIT bioengineer Dan Anderson, collaborating with Melton to build microcapsules for the beta cells, took high-volume testing to a much higher level for various capsule designs.

Over the decades, many groups have tried to encapsulate beta cells in tiny spheres of alginate. Historically, “all these capsules end up covered in scar tissue,” Anderson told the ADA session.

But after endlessly tweaking the properties of these spheres, “we have a growing list of materials we could use,” he said.

One capsule material seems to work well in mice with strong immune systems—and in very early testing in macaques. Details on the material aren’t yet public, but the secret isn’t in the material’s permeability but in how the immune system reacts to it, Anderson said.

His group’s exhaustive testing also gave clues to how capsule size affects immune scarring. Last month, he and colleagues reported in Nature Materials that 1.5-mm-diameter capsules do better than 0.5-mm structures. Was that a surprise? “It was for us,” Anderson replied. “We thought smaller would be better.”

by

Nanostepping up against cancer

Most ovarian cancer is discovered at an advanced stage, responds to standard treatments of surgery and chemotherapy, and then relapses. Unsurprisingly, the better the job of surgically removing tumors, the better the patient’s prospects.

This month in PNAS, MIT’s Angela Belcher and colleagues described a near-infrared imaging system based on an injected nanodevice combining carbon nanotubes with peptides that latch onto ovarian cancer cells, assembled neatly via synthesized bacteriophage virus. In an early surgical test on mice, the technique proved very effective at detecting tiny clumps of cancer cells.

Presenting her work last week at an ovarian cancer event at the Koch Institute for Integrative Cancer Research, Belcher noted that this imaging technique currently works through about 10 cm of tissue, which covers a lot of territory in the human body. She hopes that the method can be extended to gather molecular information about tumor cells that could aid in treatment.

Also at the Koch event, which drew a mix of survivors and researchers, Belcher’s MIT colleagues Sangeeta Bhatia and Paula Hammond presented their ongoing work on cancer nanotherapies.

Bhatia and co-workers are developing nanodevices in which various types of short interfering RNAs (siRNAs) designed to attack cancer tumors can be wrapped inside peptides configured to penetrate tumors and pass through cell membranes. Years of painstaking work are paying off in dramatic results in mice models.

Hammond and her research partners take another approach to cluster-bombing cancer (see cartoon below). They assemble nanoparticles layer by layer, starting with a core of doxorubicin or another chemotherapy agent, adding layers of siRNAs and topping off with a “stealth” outer wrapping meant to let the nanoparticles glide through the body until they can glom onto cancer cells.

All very promising, all in early animal research, and the survivors at the Koch event kept politely asking when each advance might reach humans. “We’re still vertical,” one survivor pointed out.

Hammond_NP

by

Mind the gap, manufacturers

Say you’re a professor at a major research university. You’re brilliant, of course, and well-funded. Some of your well-guided hotshot grad students and postdocs create a technology that shrieks out for commercialization, and the university’s intellectual property folks plunge into patenting.

Maybe the hotshots then get together with a veteran executive or two and sell the idea to a venture capital firm. Their startup is off and running, and the world awaits with joy.

Or maybe the venture capitalists are otherwise occupied that month, the hotshots wander off to the next great opportunity and the idea sits on the shelf.

All too often, professors tell me, the major manufacturers who might really exploit the technology show no interest in bringing it to market from that stage. Their development ecosystem doesn’t work like that—they want to buy the startup when it has shown progress commercializing the work. They want not just patents but people, understandably enough.

This does make you wonder, though, whether more manufacturers should consider extending their own research groups a little further down the food chain to cherrypick a few of the best available intellectual properties and bring them forward much as a startup would. Maybe a few million dollars invested in this form of intrapreneuring would pay off very, very well down the road.