CAR-T: Maybe It’s Time to Change the Engine
Craig Mosman
CEO at NanoKar Therapeutics | Biotech Investor & Advisor
August 26, 2026
Every CAR-T therapy approved to treat cancer has run on the same engine.
Not similar. The same.
That engine, in CAR-T, is called the ITAM sequence. It’s a short sequence of amino acids that tells the T-cell exactly how hard to fight, how long to stick around, and whether to burn out fast or stick around to become a long-term memory cell in the patient.
It actually has a foundation that goes back more than 30 years. The ITAM sequence disclosed in a CAR-T patent granted in 1994 is the precise sequence used in the first CAR-T treatment approved by the FDA in 2017.
Furthermore, it’s the exact same ITAM sequence used in every CAR-T product in the market today.
Thirty-plus years of science. Zero changes to the engine.
Here’s why that should stop you cold: CAR-T therapy is one of the most remarkable achievements in modern medicine. We literally taught the human immune system to hunt cancer cells like a guided missile.
But the results still aren’t good enough. Current therapies carry significant toxicity risk. Severe CRS rates reach 48% in some approved-product trials, and CRS remains a boxed warning across the class. 30%-60% relapse. And zero solid tumor treatments have been approved.
For three decades, researchers have upgraded almost everything about CAR-T: better targeting, better receptors, costimulatory molecules, faster manufacturing.
Everything, that is, aside from the one component that actually decides how the cell behaves once it finds the cancer.
Think of it this way: you can upgrade the body of a car endlessly — better aerodynamics, better tires, better lights, and on and on — but if you never touch the engine, you’re still driving a 1994 model.
Toxicity. Persistence. Relapse.
All three of the field’s biggest unsolved limitations trace back to this one piece of signaling machinery.
And it’s been untouched since before Google existed.
So a University of Utah immunologist asked the question nobody else was asking: What would happen if we changed the engine?
Matt Bettini , founder of NanoKar Therapeutics, didn’t accept ITAM as a fixed part of the architecture. He tested it. 26 different ITAM configurations. Patent applications were filed.
The early finding is of the kind that changes an entire field: Change the engine, change the result. Different configurations produce different behavior: different persistence, different survival, different formation of the memory cells that make a therapy longer lasting.
Right now the industry’s biggest bets are on getting the same 30-year-old engine to more patients, faster:
· In vivo CAR-T — building the CAR inside the body instead of in a lab
· Allogeneic CAR-T — “off the shelf,” made from donor cells in advance
Both are genuine breakthroughs. Both will save lives sooner. But here’s the uncomfortable question underneath them: even if I can deliver a 1994 engine faster and cheaper, don’t I still get a 1994 result?
NanoKar’s bet is that the platform, the engine, underneath all of it — approved therapies, in vivo, allogeneic, all of it — can be upgraded at the source. An engine redesigned from the ground up.
This isn’t about abandoning 30 years of progress. It’s about asking whether the machine we’ve spent 30 years perfecting has been missing its most important upgrade the whole time.
The chassis has evolved. The engine hasn’t. Maybe it’s time to change that. 
https://www.linkedin.com/pulse/car-t-maybe-its-time-change-engine-craig-mosman-egyfc/