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When Onyx caught up with Bruce Levine in Dublin, his memory of the first patients to be treated with what would become Kymriah was still vivid: "pounds, kilograms of leukemia" obliterated by engineered T cells over a few weeks, in a 2010 adult chronic lymphoid leukemia trial. The result was so striking that the team initially mistrusted it. Nearly nine years on from Kymriah’s approval, roughly 10,000 patients have been treated with the therapy, and Levine has spent that time keeping a running wish list of how to make CAR-T better – more potent, more controllable, more durable, across more targets.
Three of the items on that list are already starting to move from wish to data. CAR-T for autoimmune disease is producing surprisingly long remissions because B-cells return and reset the immune system, not because they are permanently eliminated. In vivo CAR-T and, ultimately, in vivo gene editing using targeted lipid nanoparticles in immune cells would unlock wider patient access at a much lower cost of goods than ex vivo manufacturing – and Levine sees autologous, allogenic and in vivo approaches coexisting, not replacing one another. Solid tumours remain stubborn for well-understood reasons – heterogeneous antigens, immunosuppressive microenvironments, dense matrices – but armoured CAR-T cells and direct intratumoural injection in brain cancers are giving real, if still early, signals. Levine, a former ISCT president, also reflected on how the society has roughly tripled in size since 2018, filling the Dublin Convention Centre with 800 posters this week.
Watch the full interview above.
A special thanks to our Onyx Live sponsor:
Cellares – Automated cell therapy manufacturing at scale. https://cellares.com/
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