Dive Insight:

The search for alternatives to personalized CAR-T cell therapies like Novartis’ Kymriah and Gilead’s Yescarta has led drugmakers to pursue different strategies.

Allogene and CRISPR Therapeutics, for example, are nearing pivotal trials of “off-the-shelf” treatments that harness T cells, the same immune defenders involved in Novartis’ and Gilead’s drugs. Fate Therapeutics and Nkarta are developing therapies that use “natural killer” cells, which are part of the body’s initial attack against invaders. Both approaches have shown promise against certain blood cancers, but questions remain about how well they match up versus CAR-T and how long their effects might last.

Adicet, by comparison, is one of a cluster of companies working on “gamma delta” T cells, a subset of T cells that share elements of both innate and adaptive immunity. These cells have slight, but important, differences from other T cell types that could make them less likely to trigger graft-versus-host disease, a concern with off-the-shelf treatments that involve cells from donors. They also have the potential to recognize a range of targets and can persist in the body for years, suggesting they might be able to broaden cell therapy’s reach and trigger durable responses.

Drugmakers appear interested in tapping that potential. Takeda has acquired two gamma delta cell therapy developers over the past year. Bristol Myers Squibb partnered with Century Therapeutics in January in a deal worth as much as $3 billion. Johnson & Johnson has been aligned with Lava Therapeutics since 2018, and Regeneron licensed an Adicet program for solid tumors two years before.

As with other companies testing off-the-shelf approaches, Adicet still has much to prove. While the responses it’s reported are in heavily pretreated patients, including one whose disease progressed after CAR-T treatment, larger tests with longer follow-up are needed to determine how safe treatment is and how long responses might persist.

Allogene and CRISPR, meanwhile, started evaluating multiple-dose regimens after finding the benefits of their off-the-shelf treatments didn’t seem to last as long as those of CAR-T. Allogene’s program has also been slowed by safety concerns.

Adicet will hold a conference call on June 6 to discuss the updated results being presented at ASCO.