SOHO 2025 | Moving next-generation CAR constructs into ALL therapy
Bijal Shah, MD, Moffitt Cancer Center, Tampa, FL, shares his excitement around the potential of moving next-generation CAR constructs into acute lymphoblastic leukemia (ALL) therapy. Dr Shah mentions the development of bispecific, tandem, armored, and in vivo CARs, which eliminate the need for manufacturing. Dr Shah highlights the promise of these innovative approaches, which may offer improved functionality and rapid treatment options. This interview took place at the 13th Annual Meeting of the Society of Hematologic Oncology (SOHO 2025) in Houston, TX.
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Transcript
There’s so much to be excited about when we talk about CAR T-cell therapy, not just with our current constructs, but with the constructs that are coming. There’s a 19/20 bicistronic CAR that KITE is developing, which I’m hoping will make its way into the ALL space. We’re also going to see similar tandem CARs from J&J. They bought one from a Chinese group, I think it was called [unintelligible], I’m not sure what the name is now...
There’s so much to be excited about when we talk about CAR T-cell therapy, not just with our current constructs, but with the constructs that are coming. There’s a 19/20 bicistronic CAR that KITE is developing, which I’m hoping will make its way into the ALL space. We’re also going to see similar tandem CARs from J&J. They bought one from a Chinese group, I think it was called [unintelligible], I’m not sure what the name is now. There’s another one from Miltenyi that I know is being explored in mantle cell lymphoma, and hopefully we’ll start to see some of that data in other lymphomas as well, and ALL, right? ALL also expresses CD20, and so my hope is we’ll see something there. There are 19/22 CARs that are also being explored and developed by various groups, and so we’re going to start to see some of the antigen piece of the puzzle being addressed.
And then we got to come to the next phase, right? How are we going to make… I consider the antigen piece maybe CAR 1.5. How are we going to do CAR 2.0? Meaning really constructing a better CAR, one that’s more functional. And there’s some hints, right? We’re starting to develop some of these armored cars, ones that produce cytokines like interleukin 18 that are at least… They’re very early, but showing some preclinical… sorry, some early clinical outputs that look interesting, look exciting.
We’re also moving rapidly into the space of in vivo CARs. So taking the whole manufacturing piece out of the puzzle, coming up with that construct that we literally just infused. And there was really, really interesting data in the myeloma space. It was published in The Lancet, I want to say two or three months ago. Four patients, if I recall, got an in vivo CAR. It expanded, it generated deep remissions. There was no manufacturing, it was the liposome with the instructions for making CARs embedded in it. And so I think some of these approaches are things that we’re going to likely see move their way into the ALL space because here’s a place where time is your enemy. You don’t want to allow those blasts to grow at all if you can. You want to really come in in that low disease burden setting to optimize your outcomes.
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