An anti-cancer cell therapy platform utilizing ex vivo physiologic dendritic cells expressing mRNA-encoded antigens and immune checkpoint blockers

Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

Therapeutic vaccines have struggled to effectively combat cancer. The core challenge lies in generating a durable and diverse immune response capable of eradicating tumors. The limited clinical success of therapeutic vaccination attempts highlights the need for new strategies that combine robust T cell memory induction with immune checkpoint blockade (ICB) delivery at the antigen presenting cell (APC)-T cell interface. To address this, we utilized "physiologically induced dendritic cells (phDCs)," a clinically validated APC phenotype generated via platelet P-selectin engagement of monocyte PSGL-1. Human and murine phDCs were transfected ex vivo using lipid nanoparticle (LNP) formulations with mRNA encoding antigens and cell-surface-anchored ICB antibodies, creating “armored” phDCs. Intravenous administration of these phDCs stimulated antigen-specific T cells, suppressed tumors, and generated long-term immune memory in murine cancer models. Moreover, in an autoimmune NOD model, where anti-PD1 accelerates type-1 diabetes, serial systemic treatments with anti-PD1 "armored" phDCs failed to induce disease onset. These findings demonstrate the potential of mRNA “armored” phDCs to drive anti-tumor efficacy via potent stimulation of immune responses and deliver of ICB antibodies with significantly reduced immunotoxicity.

Article activity feed