ASH 2021 | The role of myeloid cells in CAR-T cell therapy
John DiPersio, MD, PhD, Washington University School of Medicine, Saint Louis, MO, discusses the how the presence of myeloid cells enhance chimeric antigen receptor (CAR) T-cell activity. He talks on producing an in vitro model based on NSGS mice injected with human cord blood cells and how myeloid cells were found to positivity affect CAR T-cell activity, despite their perceived suppressive nature. Prof. DiPersio consequently suggests further research to elucidate which classes of myeloid cells provide a positive impact on CAR T-cell therapy. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
We’ve been interested in targeting various kinds of tumors with CAR-T. And so, one of the limitations is that there’s no good mouse models. And so we’ve developed some mouse models where we’ve been able to engraft NSG-S mice. These are mice that have no immune system, but also make human cytokines. So they support human hematopoiesis. We graft these mice with human cord blood stem cells, and they grow up in the mice and become B cells, T-cells, and myeloid cells in the mouse...
We’ve been interested in targeting various kinds of tumors with CAR-T. And so, one of the limitations is that there’s no good mouse models. And so we’ve developed some mouse models where we’ve been able to engraft NSG-S mice. These are mice that have no immune system, but also make human cytokines. So they support human hematopoiesis. We graft these mice with human cord blood stem cells, and they grow up in the mice and become B cells, T-cells, and myeloid cells in the mouse.
And when we use that model, we can show specifically that when we target any kind of malignancy using any CAR that the presence of those myeloid cells in the product in grafted animals or in an in vitro model are critical to enhance the activity of the CAR-Ts. So the efficacy of CAR-Ts is very positively impacted by these myeloid cells.
And so we know for instance that the prevailing winds is that these myeloid cells are suppressive, but this study shows that there’s a population of myeloid cells that are actually supportive of CAR-T cell activity and enhanced CAR-T cell activity. So the key in the future will be to dissect which myeloid cells are really providing this supportive environment and which ones are suppressive. But these initial studies show in contradiction to many of the previous papers that the myeloid cells provide a supportive environment for increased CAR-T cell activity.
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