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ASH 2025 | Pre-manufacturing CD8+ central-memory type 2 T-cells predict axi-cel failure in LBCL
In this video, Joseph Melenhorst, PhD, Cleveland Clinic, Cleveland, OH, discusses his work identifying a baseline pre-manufacturing central memory CD8+ T-cell signature that acts as a robust predictor of resistance to 28ζ-based CAR T-cell therapy with axicabtagene ciloleucel (axi-cel) in large B-cell lymphoma (LBCL). This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
So that’s quite a surprise finding. In collaboration with Suman Mitra and Franck Morschhauser in Lille in France, we set out to do a very similar study using very similar tools, including single-cell RNA sequencing on baseline samples and the infusion product and post-infusion. And my main interest really is to see if we can find anything before a product is manufactured, like I published in 2018 with Joe Fraietta when I was at Penn...
So that’s quite a surprise finding. In collaboration with Suman Mitra and Franck Morschhauser in Lille in France, we set out to do a very similar study using very similar tools, including single-cell RNA sequencing on baseline samples and the infusion product and post-infusion. And my main interest really is to see if we can find anything before a product is manufactured, like I published in 2018 with Joe Fraietta when I was at Penn. There was a paper in Nature Medicine. And we found actually with axi-cel, which co-signals us through CD28, that the signature that predicts a BBζ CAR response predicts non-response with the 28ζ CAR. And that was a quite surprising finding. That’s a poster that I’ll be presenting here at ASH. And furthermore, we found that a factor in effector memory signature in pre-manufactured cells predicts the response to an axi-cel product. So it’s very exciting on multiple levels, but it gives us a way to predict which product would actually work best for a patient, and also tells us how we can then modify the manufacturing process.
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