The gamma delta T cell gambit inspires a small London biotech startup with big ideas
If you run through the whole gamut of cell therapies being worked on in cancer research these days, gamma delta T cells aren’t likely to figure prominently in your review. But for years now Adrian Hayday, who runs labs at The Francis Crick Institute and King’s College London, has been fascinated by their unusual ability to penetrate into tissue, making them potential therapeutic candidates.
And now, with the explosion of immuno-oncology research work, some marquee research players have set out to take Hayday’s work — along with contributions by Oliver Nussbaumer — into the clinic, seeding a startup which will now navigate its way through about 18 months of preclinical work identifying a lead program that can be taken into a human study.
The startup, appropriately dubbed GammaDelta Therapeutics, is being helmed by Raj Mehta from Cancer Research Technology, who’s taking a break from his business development role to act as the interim CEO of a small band of staffers, in league with Hayday’s big lab, to start piecing together all the early-stage work needed to get their work to the threshold of Phase I. CRT, along with King’s College and The Crick, are providing assistance. Tim Haines, the managing partner at Abingworth’s London office, is contributing seed cash and incubating the company.
What’s the big idea? It’s very simple.
Gamma delta T cells “have the potential to invade tissue and be better at invading tumors,” Mehta tells me. And that makes it a potential groundbreaker in all the immuno-oncology work now going on globally.
Where the checkpoint therapies like Keytruda and Opdivo require an environment with a heavy mutation load to be effective, gamma delta cells – at least in the preclinical work — don’t. And where CAR-Ts — T cells which have been reengineered with chimeric antigen receptors — have proved promising initially in blood cancers, it’s been a challenge getting them into tumors. (And, yes, there’s a lot of work being done to fix that.)
Gamma delta cells, though, have the essential properties to get inside tumors to do their work. Also, these cells evidently aren’t heavily influenced by regulatory T cells, making them good candidates for solid tumors with high concentrations of Tregs.
One of the biggest challenges faced by the fledgling biotech, says Mehta, will be figuring out the CMC side of things. These therapies won’t be very valuable if they aren’t potent, durable and fairly straightforward to make. But the team also has a big advantage: London has emerged as a global hub for cell manufacturing, making their job somewhat easier on that score.
The emphasis here is on the collaboration among the research institutes, with the venture backing from Haines’ venture group. They’re not saying how much it is costing at this point, but chances are it’s not the kind of figure that would leap out at you with all the big numbers being thrown around biotech these days.
Mehta is familiar with at least two other European companies that have been operating in this field. Lymphact in Portugal is one. And there’s also Gadeta, a Dutch biotech which just raised 7 million euros in a round led by Medicxi Ventures. Gadeta has been using gamma delta T cell receptors to reengineer the more common type of T cells.
GammaDelta has a distance to travel before it gets close to putting anything into Phase III. But in the intense I/O field right now, it will likely start attracting immediate attention from some key players.