Is it 'science fiction'? No: Researchers want immune cells to find cancer and report back

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Nov 3

Our immune cells are constantly circulating through our bodies, killing off cancer cells before they grow into something worrisome.

Now a consortium, including Yale University, underwritten by Facebook founder Mark Zuckerberg and his wife, Priscilla Chan, is focused on programming those cells to more efficiently prevent disease.

It's the country's third BioHub, following San Francisco and Chicago, and it will combine the scientific resources of Yale, Columbia and Rockefeller universities, financed by the Chan Zuckerberg Initiative.

"It sounds a bit science fiction when you first hear about it, but at the same time it's also very grounded in solid science," said John Tsang, Yale's lead on the project and director of the Yale Center for Systems and Engineering Immunology.

"Immune cells are unique in that they go around your body, they are circulating, they go into tissues, they can detect issues in your tissues, for example, without us knowing," Tsang said.

That includes cancer cells, he said.

"Typically we believe that our immune system is taking care of those for us already so they typically don't grow out," he said. "But the process of how that works, it's not really well understood. We know that the immune cells are doing some of that, and the immune cells are also going around and sensing other things."

The challenge for the scientists in the BioHub, which eventually will be a brick-and-mortar center in Manhattan, is how to use the immune cells "as a programming device," Tsang said.

Andrea Califano, chairman of the Systems Biology Department at Columbia, leader of the New York BioHub, called the engineered immune cell a "cellular endoscope."

"It will actually be not invasive at all," he said. "It will be one of your own cells that has been changed a little bit to go to a particular organ and to detect whether there's, for instance, a tumor that would be very easy to treat, if it were detected early but will be actually be very difficult or even impossible to treat if it's caught later."

Examples are pancreatic cancer and glioblastoma, which "are on the top hit list of what kills human beings."

The plan is to "program the cells in a way that (they) can now go into your liver go in through a gut, and then they can be sensors of those issues and report back to us on what's going on, and also potentially the cells can actually do something in those tissues as well … specifically to our liking," Tsang said.

"We get tumors basically a million times a day," Califano said. "The immune system just wipes them out before they're harmful, but how do they wipe them out? Because when cancers have mutations those mutations are not recognizing it as a cell that is part of your body so the tumor detects that and kills the cancer cell."

But cancer cells also recruit nearby immune cells, which prevent other immune cells from attacking the tumor "so the tumor is very good at emitting signals that will recruit cells or reprogram cells that are now becoming immunosuppressive, he said. "They no longer allow the immune system to think the cancer is a bad thing, basically hiding behind a cape of invisibility."

The BioHub team's job is to program immune cells to recognize the signals sent out by the protective cells.

Some immune cells prefer to go into certain organs better than others, so Tsang wants to decode what he calls "cell trafficking."

"And then once we understand that, then we can use that knowledge to engineer the cells," he said. "For example, let them express certain types of genes that will then go into specific locations."

Immune cells could also be used to insert DNA into specific places into the genome, using CRISPR technology, which edits genes, that would guide immune cells into specific locations.

"And they can then sense the kind of events we want them to sense," Tsang said. "They could be sensing for example, specific signals in the early tumor, and then that signal gets into the cell, which would then guide the cell to do other things."

The third technology is called writing, "how do you write information within the cells like it's like writing to a tape?" he said.

The team is a long way off from being able to have immune cells perform these tasks, Tsang said. There are challenges in both basic science and engineering to be met.

Chan Zuckerberg has committed $250 million over 10 years to the project.

"I think it's scientifically very exciting; it's challenging," Tsang said. "But of course, you need to get the right teams and getting all the people together and I think that's part of the excitement but it's also part of the challenge."

Tsang said he's also excited about getting together with colleagues from Columbia and Rockefeller. "I think a new spark would come out even beyond what you envision in terms of these specific goals," he said.

"You get a bunch of people together and with this being the glue and the catalyst for getting the folks together, I think we're going to advance both on the front that we can see now but also there will be unexpected new things I think that would come up," he said.

"The collaborative nature of this effort is really remarkable because this is something that, when I was originally exposed to the idea I thought it was science fiction, and there was no way we're going to be able to do it," Califano said.

"And then when we started to go around the three institutions, we saw that all the individual pieces were actually there. And so this is something that cannot be done by any institution in isolation, and I think that's what makes it truly remarkable," he said.

Ed Stannard can be reached at estannard@courant.com.