Low-Strength Type I Interferon Signaling Promotes CAR T-Cell Treatment Efficacy

However, up to 60% of patients do not achieve a complete response. In this study, we analyzed the infusion products of eight r/r DLBCL patients with distinct clinical responses to axicabtagene ciloleucel using single-cell transcriptomics.

Compared to patients with progressive disease, infusion products of complete responders demonstrated stronger signatures of type I interferon (IFN-I) signaling and cytotoxicity. Based on these findings, we developed a novel strategy to improve CD19-directed CAR T-cell treatment efficacy by incorporating IFN-I during the ex vivo manufacturing process. While high-strength IFN-I signaling increases both CAR T-cell cytotoxicity and apoptosis, low-strength IFN-I signaling selectively enhances CAR T-cell cytotoxicity without compromising viability.