Cell therapy player GammaDelta spins off Adaptate to direct body's surveillance system
If alpha beta T-cells — the foundation of CAR-T cell therapy — are “killer cells,” trained in the biologically ancient art of executing intruders, think of their gamma delta cousins as armed guards, capable of engaging an interloper but also of sounding an alarm to kick the rest of the body’s defenses into action.
“The key role they play is to conduct immune surveillance,” Natalie Mount told Endpoints News. And once they find an intruder “they can stimulate a whole immune response as well as be cytotoxic [cell-killing].”
Only discovered in 1985, these gamma delta T-cells (γδ) have already become a popular target in cancer immunotherapy. This morning, a top British biotech exploring potential γδ applications founded a new company to help reach that goal as GammaDelta Therapeutics spun off Adaptate Biotherapeutics with Mount at its helm.
While GammaDelta will continue to focus on a CAR-T-like cell therapy approach, the new company will develop antibodies that guide the γδ cells as they patrol a patient, Mount said. Both have the same aim: getting these cellular guards to notice and effectively strike cancers.
“We are developing antibodies that are able to recognize the gamma delta cells and target those and modulate their activities,” Mount said. “We’ve discovered a range of substrates and what we can do now is take that forward in non-clinical development.”
Gamma delta cells have risen in popularity in oncology research largely because they show potential to bring cell therapy’s effectiveness in blood cancers to solid tumors, although they present other potential advantages, including broader targeting and faster response.
GammaDelta Therapeutics got in on the ground floor, opening its doors in 2016. Since then, new and bigger players have entered the game. Last week, Regeneron dropped $25 million as part of an $80 million funding round for Adicet Bio, another company looking to use antibodies to guide gamma delta T cells.
“Just in the last 2 to 3 years there’s been a real solid interest,” Mount said.
The broad idea of targeting these cells for oncology is not new. Clinical trials have been conducted evaluating gamma delta T cell treatments on several cancers, including leukemia and sarcoma. They were safe but with highly limited efficacy, although some appeared for not-fully-understood reasons to actually fuel tumors.
But GammaDelta and Adaptate say they work on a different subset of cells than these earlier trials did, one called γδ1. γδ1 is found in the tissues, making it an intuitive weapon for attacking solid tumors.
The antibody concept behind Adaptate is an increasingly popular form of therapy. AbbVie, Eli Lilly, Regeneron, and Sanofi, among a long list of others, are developing a form of antibody therapy called bispecific. They’re still in the early stage, but last year Baird’s Brian Skorney argued that the class of drugs has huge potential.
“Our bias is that bispecifics pose an existential risk to the cellular therapies,” he wrote. “If a regularly administered therapeutic can keep anti-tumor pressure on by consistently engaging and activating T-cells, we think the much more expensive CART would become an even harder sell than it already is.”
The exhaustive CAR-T process is like a specialized masterclass in tumor-killing, with doctors withdrawing cells, equipping them with a specific antigen receptor to identify malignancies and re-injecting them. The antibody approach for Adaptate can be thought of more as directives from a command center guiding the surveilling immune cells.
GammaDelta will focus on a cell therapy process similar to CAR-T, while Adaptate focuses on antibodies. But Mount argued one of the big advantages for GammaDelta Therapeutics and gamma delta cells is that they can identify cancer cells based on patterns as opposed to the specific antigens that CAR-T (chimeric antigen receptor T-cells) therapies use, opening up the potential for a range of targets.
GammaDelta is much closer to the clinic than the Adaptate spinoff, although they have yet to reveal exactly when they will begin trials, and for what indications. Mount said they were at least 12 months from evaluating whether they were ready to enter the clinic.
Social image: Adaptive CEO Natalie Mount via GammaDelta