IL-12-producing iPSC-derived antigen-presenting cells enhance antitumor immunity and enable off-the-shelf immunotherapy.

Abstract

Effective activation of cancer-reactive T cells by antigen-presenting cells (APCs) is essential for tumor elimination. However, dendritic cell (DC)-based cancer vaccines often yield inconsistent clinical outcomes due to patient-dependent variability. We established IL-12-producing proliferative myeloid cells (IL12-pMCs) from mouse induced pluripotent stem cells (iPSCs) as a standardized APC platform. These cells stably secrete IL-12, express costimulatory molecules, and enhance the priming and expansion of antigen-specific CD8+ T cells, while also activating NK cells. Upon tumor antigen loading and in vivo administration, IL12-pMCs induced robust IFN-related gene signatures in tumors, promoted infiltration of effector cells, suppressed immunosuppressive populations, and showed potent antitumor efficacy, with further enhancement when combined with immune checkpoint inhibitors (ICIs). For clinical application, we generated human IL12-pMCs from iPSCs with selective HLA expression to enable antigen-specific CD8+ T cell priming while minimizing alloreactivity. This system offers a potent, off-the-shelf APC platform for next-generation cancer immunotherapy.