ISAL 2023 | Insights into NKG2D-targeting CAR-T cells in R/R AML

Yeah, so we just published our paper in Lancet Hematology. I think we all know in CAR-T development in AML that there’s not going to be a singular antigen that we can target, so we don’t have our CD19, we don’t have our BCMA. So what’s attractive about either NK cells or an NKG2D CAR and T-cells is basically it’s agnostic to a specific antigen. So it recognizes a whole family of either MYC-A/MYC-B or ULBP antigens and usually all blasts express these. So I think it’s kind of exciting in that it again is agnostic to a specific antigen. I think the challenge is there may be differential expression on leukemic stem cells versus blasts. Actually a nice presentation yesterday at this meeting kind of nicely showed that the ligands are often absent on the actual leukemic stem cell but you can maybe induce them. For example, PARP inhibitors in the presentation yesterday were able to induce those. I think in our study we did see that it was overall safe. We were able to complete the Phase I, get through dose level three, and we did see activity particularly in patients with lower blast counts. We had some patients bridge to transplant who had very durable outcomes and some responses in other patients. But outside of getting the patients to transplant, the responses were non-durable. There are several steps being forward. There is sort of ongoing work looking at NKG2D, but I think again, not enough efficacy which has really been a challenge to date across CAR-T development in AML.