to look at in a high-volume, systematic way ever before. It creates a staggering diversity of possible ways humans respond to infection. For scientists trying to pinpoint the cause of, say, autoimmune disease, this also creates a classic needle-in-a-haystack problem.
Adaptive TCR hopes that by sequencing lots of blood samples from different individuals, and using its proprietary software, they can find some commonalities in the kinds of T-cell receptors that people form in certain situations, whether it is responding to a foreign pathogen like flu, or turning the immune system’s natural firepower on healthy tissue, like it does with rheumatoid arthritis. If scientists could find signature proteins on T-cells at the root of these immune system irregularities, then they could incorporate that knowledge into diagnostic products or use it to identify drug targets, Adaptive TCR says.
Few scientists have tried to look at these T-cell receptors in a high-output fashion before. Fewer than 30,000 T-cell receptors had been sequenced with conventional methods before the Adaptive TCR technique came along, Chad Robins says. The Adaptive TCR method claims to be able to identify 100 million T-cell receptor sequences over a four-day period.
The high-volume screening technology from Adaptive TCR “provides a sensitive and specific tool” for measuring patterns of T-cell variation, with “more resolution compared to techniques that we’ve used in the past,” says Nepom, the director of the Benaroya Research Institute. Chad Robins described it with an analogy: “These guys have invented the Hubble telescope compared to what we used to have, a pair of binoculars.”
So how is this supposed to become a business? It is starting out as a fee-for-service provider to academic and industrial customers who want to look at the diversity of T-cells. People ship their samples to Adaptive TCR’s offices, and get back a result on the T-cell diversity and repertoire from the sample. Adaptive isn’t spending big money on its own servers to host this data—those gigabytes are being stored on secure remote servers operated by Amazon Web Services.
The fee-for-service model can certainly generate revenue early on to sustain the company, but that’s not the end of the story.
Adaptive TCR has some other ideas on how to capture more of the future value that this data on T-cells might create for diagnostics and drug discovery. Autoimmune diseases—in which the immune system goes haywire and starts attacking healthy tissues like a virus—affect an estimated one out of every 12 people in the U.S. with more than 80 different conditions, according to the National Institutes of Health. They are notoriously hard to diagnose, because there’s not a good molecular tool for that, Robins says. By getting high-resolution looks at T-cell receptors, Adaptive TCR hopes to find some of the basic immune system malfunctioning at a molecular level that hasn’t been seen before, which could provide for much earlier diagnosis.
While there is a huge amount of variation in the genetics of T-cell receptors in one individual, Adaptive TCR also thinks it’s possible that there are overlapping stretches of DNA in these T-cell receptors shared between patients with an autoimmune disease like Type 1 diabetes or multiple sclerosis, Robins says. The company has a collaboration with Nepom’s team at the Benaroya Research Institute to look for those overlapping stretches, which could become valuable new drug targets.
Of course, these are still early days at the company. Harlan Robins and Chris Carlson are keeping their faculty positions at the Hutch. Much will depend on whether the early customers think they are getting their money’s worth by getting all this data on T-cell diversity over the coming year. Proof to show the value of the method will take time to emerge in peer-reviewed literature. The founders, whom I met a few weeks ago during a visit to the Hutch, didn’t sound like they are getting too carried away with themselves yet.
“These guys came up with this, and it’s my job not to screw it up,” Chad Robins says. “They’ve invented something extraordinary, but the invention still needs to be brought to the market.”
