Technology Description

Plasmacytoid dendritic cells (pDCs) are rare but highly potent immune cells that play a critical role in initiating innate and adaptive immune responses. Upon activation, pDCs produce large amounts of type I interferons, including interferon alpha (IFN-a), which drive downstream activation of multiple immune effector populations. Therapeutic strategies that activate pDCs have shown promise in cancer immunotherapy and vaccine development, including in situ tumor immunization and vaccine adjuvant applications. However, current approaches for delivering immune stimulants to pDCs remain suboptimal, limiting their clinical impact.

Researchers at the University of Iowa have developed a novel nanoparticle-based delivery platform that enhances pDC activation through targeted delivery of Toll-like receptor 9 (TLR9) agonists. These immunostimulatory nanoparticles are coated with heparin and are engineered to engage BDCA2, a receptor selectively expressed on pDCs. While BDCA2 signaling has historically been associated with suppression of pDC activation, this formulation uniquely leverages BDCA2-mediated uptake to deliver TLR9 agonists intracellularly, resulting in robust pDC activation rather than repression.

In vitro studies using human peripheral blood mononuclear cells demonstrate that these nanoparticles induce a strong pDC activation phenotype and significantly increase production of IFN-a. This targeted and potent immune activation supports the use of this platform as a next-generation immunostimulatory technology.

UIRF Case No. 2025-010

Stage of Development

The nanoparticle formulations have been evaluated in vitro using human peripheral blood mononuclear cells. Ongoing studies are focused on optimizing particle composition and advancing lead candidates toward in vivo evaluation.

• Potent immune activation observed with initial dosing in vitro.
• Enhanced immunostimulatory activity with increased heparin surface density.
• Broad applicability across oncology immunotherapy and vaccine adjuvant development.
• Potential to improve efficacy while reducing required antigen or adjuvant dose.