IL-18-armored CAR T Drives Remissions in Relapsed B-Cell Leukemia

In an onsite interview with CURE at the 2025 ASH Annual Meeting, Dr. Matthew P. Connor, assistant professor of Clinical Medicine at Penn Medicine, discusses a new generation of CAR T‑cell therapy designed to improve outcomes for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL).

Standard CD19‑directed CAR T therapies induce high remission rates, but relapses remain a major challenge, especially in patients heavily pretreated or with central nervous system (CNS) involvement.

Connor explains how huCART19‑IL18, an “armored” CAR T‑cell that secretes interleukin‑18 (IL‑18), is meant to enhance immune activity and potentially deepen remissions compared with conventional CD19‑targeted CAR T cells. In an early first‑in‑human clinical trial, all treated patients with adequate follow‑up achieved MRD‑negative complete remissions, including in the CNS, with manageable toxicities and no relapses or deaths at a median 15‑month follow‑up.

These findings may support the potential of IL‑18‑armored CAR T cells to improve durability of response in patients who have relapsed after multiple prior therapies.

Transcript

How would you explain what IL-18-armored CAR T-cells are? What makes this approach different from the standard CD19-directed CAR T-cells?

CAR T-cells, as you may know, are a patient's own immune cells that we take, manufacture and give back to a patient who has some kind of hematologic cancer to help fight that cancer with their own immune system. IL-18-armored CAR T-cells essentially take that concept and add an additional layer of support to help make those T-cells even more effective, specifically, a protein in the normal human body called IL-18 that promotes inflammation to hopefully help those T-cells fight cancer. Even better.

Patients who have leukemia and who have relapsed or progressed after prior lines of therapy are often at higher risk for not achieving long-term remissions or even cures. So, thus, it's very important for us to test novel or new, unique treatments or additions to effective treatments in order to improve the rates at which we can hopefully cure these patients.

Reference

1. “IL18-armored CAR T cells in relapsed/refractory B cell acute lymphoblastic leukemia,” by Dr. Matthew Connor, et al., 2025 ASH Annual Meeting.

Transcript has been edited for clarity and conciseness.

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