Dr Svoboda on the Investigation of huCART19-IL18 in Relapsed/Refractory Lymphoma

Jakub Svoboda, MD, associate professor, medicine, Hematology-Oncology, attending, the Hospital of the University of Pennsylvania; co-chair, Lymphoma Tumor Board and Case Conference; member, Data Safety Monitoring Committee, Abramson Cancer Center, discusses the ongoing investigation of armored huCART19-IL18 in patients with relapsed/refractory lymphomas following progression on treatment with an anti-CD19 CAR T-cell therapy.

At the 2024 ASCO Annual Meeting, Svoboda and colleagues shared that treatment with huCART19-IL18 is associated with an acceptable safety profile and elicits durable remission rates in heavily pretreated patients who have relapsed/refractory lymphoma following prior CAR T-cell therapy.

In the field of lymphoma, there are several areas needing improvement, with a significant unmet need among patients who progress after receiving currently available anti-CD19 CAR T-cell therapies, Svoboda begins. These patients, particularly those who are relapsed/refractory following such treatments, were the focus of the clinical trial presentation at ASCO, he states. The innovative aspect of this product, referred to as an armored CAR T-cell therapy or fourth-generation CAR T-cell therapy, lies in its enhancements over existing therapies, Svoboda reports. This product is an autologous T-cell therapy similar to those currently on the market, but it includes modifications aimed at improving efficacy, he adds.

One key modification is that huCART19-IL18 can secrete interleukin (IL)–18, a pro-inflammatory cytokine, Svoboda expands. Preclinical studies indicate that IL-18 boosts the cytotoxic potential of T cells and may also alter the tumor microenvironment (TME), he says. Additionally, IL-18 exhibits anti-lymphoma properties. These enhancements, combined with the specificity of the CAR targeting CD19, provide significant advantages, Svoboda elucidates. By enhancing the cytolytic capabilities of T cells and potentially improving the TME, IL-18 contributes to the product’s overall efficacy against lymphoma, he notes. This phase 1, first-in-human clinical trial (NCT04684563) explored huCART19-IL18 to address unmet needs for patients relapsing after anti-CD19 CAR T-cell therapies, Svoboda concludes.