ASH 2024 | Correlation of serum inflammatory state and macrophage phenotype with CAR-T expansion and outcomes

So that’s a continuation of a year-long kind of collaborative effort of myself and Fred Locke from the Moffitt Cancer Center, where we’ve utilized patient samples to try to understand why some patients have poor responses to CD19-targeted CAR T-cells. And what we showed is that macrophages can be enriched in patients’ lymphoma microenvironment that have poor outcomes. 

So when I moved to the Roswell Park Cancer Center, I started collecting serum samples from patients to see, is there something within the patient’s inflammatory milieu, which can be reflected by their serum, that’s accounting for this. So what we did is we took patient serum and co-cultured them with healthy donor monocytes. And what happened is these monocytes were differentiated into a very suppressive macrophage phenotype. And when we co-cultured those macrophages with CAR T-cells, we saw that the CAR T-cells were significantly suppressed. So this suggests a model in patients where their inflammatory environment is basically differentiating macrophages to be very suppressive and accounting for poor outcomes. 

So one of the big things that we’re doing now is trying to figure out, well, if the patient’s inflammatory environment is set up to be suppressive, are there medications, are there antibodies, are there cytokines that we can give to these patients to kind of reset the system to be more supportive. And those are things that hopefully we’re going to be doing some clinical trials in the next year or so to see if we can improve some of those outcomes.

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