iwCAR-T 2024 | Allo approaches in CAR-T

Frederick Locke:

Welcome to Miami for iwCAR-T 2024. Really excited to be here. My name is Fred Locke from Moffitt Cancer Center. Pleased to be here with Krish.

Krish Patel:

Krish Patel from the Swedish Cancer Institute. Happy to be with you, Fred. 

Frederick Locke:

Yeah. So we just finished up an amazing session. We talked a lot about allogeneic CAR T-cell therapy and a little bit of NK-cell therapy. What’s your impression of that session and how that went? 

Krish Patel:

Yeah, I mean, it was a really kind of dynamic session, lots of different themes. I think some of the things that were really interesting to think about were: what’s the optimal lymphodepletion? What’s the optimal platform or the patient population that we’re going to study those in? So lots of different pieces there, but I think the common theme was trying to improve access, right? Trying to decentralize cellular therapy. So we’re not there yet, but we have lots to learn from. 

Frederick Locke:

Yeah. The bottom line is we need to get patients these CAR T-cells, we need to get them quicker, and frankly, they need to be safer so we can do them beyond just these specialized tertiary centers. But one of the problems we talked a bit about was the clinical development problems. Right? So we have these really effective autologous CAR T-cells for large B-cell lymphoma and for other diseases. How do we get allogeneic CAR T-cells into patients into FDA-approved therapies? What do you think?

Krish Patel: 

Yeah, I mean, it’s a great question. You know, we know autologous CAR T-cells are curative for a subset of patients. So how do we sort of introduce a new class of therapies? I really liked the study you presented looking at, you know, a population that we can maybe preemptively treat with a different product. So maybe that pressure of immediate disease need that sort of gives us a different opportunity to bring a new class to market. So, you know, targeting perhaps residual MRD, whether that’s after frontline therapy, after an autologous CAR, or maybe both. These are all really interesting things. And then, like you said, fine tuning that balance between how do we drive up the efficacy of the allo CAR but keep them safe. 

Frederick Locke:

Yeah, that’s the ALPHA3 study, which will be launching soon, which is really looking at minimal residual disease following front-line therapy for large B-cell lymphoma, so a completion of six cycles of R-CHOP, for example. Patients who are MRD-positive are expected to be at really high risk for relapse within the next 6 to 12 months, and if you could preemptively treat those patients with an allogeneic CAR T-cell therapy, that’s probably something that patients might be willing to undergo. And so, that randomized ALPHA3 study may help to answer that. And it provides a strategy to get this therapy, potentially get it to market without competing after relapse for autologous CARs, where the resistance mechanisms are there within the tumor, within the systemic immunity of the patient, and that’s not fixed with an allogeneic CAR. 

But we also talked a bit about NK-cells and invariant NK cells and IPS. What’s your take on these strategies? 

Krish Patel:

Yeah. So I think, you know, one of the things that NK-cells maybe offer us is a different mechanism of tumor killing. Right? So they kill cancer cells in different ways than T-cells, but they can also kill cancer cells in a similar way to T-cells by introducing a CAR. So you may have this ability to potentially overcome resistance that exists from a typical T-cell mediated therapy. They also, I think this is really their main advantage, they seem to not cause CRS and ICANS. So they have a very different toxicity profile. But I think, you know, they’re very, very promising in that sense. We talked about two trials, the FT596 CD19 CAR and CNTY-101, and both of these are, I think, great proof of concept. And the field is going to continue to study these types of therapies to help us kind of figure out where is their optimal use. Persistence remains a question for NK-cells as well. Perhaps because they do have a different safety profile, perhaps we can give them more like drugs, we can give them as repeated dosing. So these are all really, I think, really kind of interesting, intriguing ways of trying to improve upon what we have from autologous cell therapy. 

Frederick Locke:

Yeah, really exciting times. We’re very hopeful that these allogeneic products make it to market. And it was a great session to hear about all the progress that’s being made. And we still have a ways to go. But we’re really excited to be here, and thank you for joining us.