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ESMO Immuno-Oncology 2025 | Unique safety challenges in modulating non-T cell compartments

Sebastian Kobold, MD, PhD, Ludwig Maximilian University of Munich, Munich, Germany, discusses the current state of clinical experience with various types of immune cells, including T cells, macrophages, NK cells, and myeloid cells. Limited but promising data available exist, particularly with NK cells, which have shown impressive response rates with lower toxicity. As the field is still in its early stages, there are concerns about toxicity and complexity, as seen with the CD47 targeted approach, which has shown encouraging results but also raised concerns about off-target effects. This interview took place at 2025 European Society for Medical Oncology (ESMO) Immuno-Oncology Congress in London, UK.

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Transcript

Yeah, I mean, so that’s a tough one, simply because up to that point, the clinical experience with T cell types is comparably limited. And this varies, actually. So if we now, if we consider the engineering part for the T cell, so non-T cell engineering part, I think we are at the level of phase one at best early phase two trial. So it’s really low numbers of patients where let’s say in the macrophage world, we haven’t received so many responses...

Yeah, I mean, so that’s a tough one, simply because up to that point, the clinical experience with T cell types is comparably limited. And this varies, actually. So if we now, if we consider the engineering part for the T cell, so non-T cell engineering part, I think we are at the level of phase one at best early phase two trial. So it’s really low numbers of patients where let’s say in the macrophage world, we haven’t received so many responses. So we don’t see much consistency, but it’s not much. So it’s the cause of the validity of these findings a bit into question. It’s different for NK cells because I think there’s been quite some exciting clinical data reported in the last three years on NK cells, mainly from Houston, from the Katy Rezvani group or clinical trial unit that has been showing quite impressive response rates, very comparable to those in lymphoma and leukemia. So indicating that these cells, these NK cells can be as effective, but way less toxic, actually, according to their reports. And I think it goes a little bit through the different modalities where we have to be very limited in our experiences so far. I think one exception may be actually the myeloid cells, where at least we’ve had some compounds that are much more advanced clinically, like the CD47 targeted approach, which is, which is meant to enhance the phagocytic function of macrophages or myeloid cells. And I think Kip Czarcinski may be talking about that on the same session. So maybe you have an interview with him for more details, but I think the bottom line of this approach that already went through several types of clinical trials showing at least encouraging results is also that there were some complexity concerns. And why is that? Because CD47 is also quite highly expressed on other types of cells, including erythrocytes and other cells of the blood lineage. So indicating that there is also a reason for caution there that although we think that targeting a specific pathway of a certain axis of the myeloid axis, efficacy in that case can also come with toxicity.

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