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ASH 2024 | Developing and testing CD371-targeted CAR T-cells secreting IL-18 for refractory AML
Renier Brentjens, MD, PhD, Roswell Park Comprehensive Cancer Center, Buffalo, NY, provides insight into the development of CAR T-cell therapy for the treatment of acute myeloid leukemia (AML), highlighting a novel armored CD371-targeted CAR T-cell product secreting interleukin-18 (IL-18) that has demonstrated robust expansion and disease clearance in a Phase I trial (NCT06017258) in patients with refractory disease. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript
So, this abstract is really exciting because it’s a new approach to CAR T-cell therapy. We’ve had a lot of success with CAR T-cells in lymphoma and other diseases, but one of the challenges has been getting them to work well in acute myeloid leukemia, or AML. And the reason for that is that AML is a very heterogeneous disease, and it’s hard to find a target that’s specific to the cancer cells and not to normal cells...
So, this abstract is really exciting because it’s a new approach to CAR T-cell therapy. We’ve had a lot of success with CAR T-cells in lymphoma and other diseases, but one of the challenges has been getting them to work well in acute myeloid leukemia, or AML. And the reason for that is that AML is a very heterogeneous disease, and it’s hard to find a target that’s specific to the cancer cells and not to normal cells.
But in this abstract, we’re using a new target called CD371, which is a protein that’s expressed on the surface of AML cells, but not on normal cells. And we’re using a CAR T-cell that’s designed to recognize CD371 and kill the AML cells.
The other thing that’s new about this approach is that we’re also engineering the CAR T-cells to secrete a cytokine called interleukin-18, or IL-18. IL-18 is a molecule that helps to activate the immune system and recruit other immune cells to the site of the tumor.
So, in this study, we treated 12 patients with refractory AML, which means that their disease had come back after previous treatments. And we saw some really impressive results. The CAR T-cells expanded very well in the patients, and we saw significant disease clearance in many of the patients.
One of the things that was really striking was that the patients who responded to the treatment had a very high level of IL-18 in their blood, which suggests that the IL-18 was playing a key role in the anti-tumor response.
Overall, I think this is a very promising approach, and we’re excited to continue studying it in larger clinical trials.
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Disclosures
Triumvira, Cargo Tx, CoImmune: Membership on an entity’s Board of Directors or advisory committees; BMS: Research Funding; BMS, Caribou, Sanofi: Other: licensed intellectual property to and collects royalties from; BMS, Atara Biotherapeutics Inc. and was a consultant for Triumvira, Cargo Tx, CoImmune: Consultancy.
