Innate-immune activating nanoparticles for cancer treatment

The National Cancer Institute awarded the Regents of the University of Michigan $669,421 on July 20, 2026, under the Cancer Treatment Research program (CFDA 93.395) to develop innate-immune-activating nanoparticles for cancer treatment.

The funded work applies bioengineering principles to design STING-activating nanoparticles that overcome limitations of current cyclic dinucleotide-based STING agonists, including poor intracellular uptake, rapid in vivo degradation, and restriction to intratumoral injection routes. The research evaluates efficacy and safety of the proposed nanoparticles in murine tumor models and companion dogs with naturally occurring cancer, assessing systemic immune responses, nanoparticle distribution, therapeutic efficacy, and toxicity. The project runs through June 30, 2031, with place of performance in Ann Arbor, Michigan.

The award is classified as a Project Grant, an assistance type supporting investigator-initiated research. The Cancer Treatment Research program develops and evaluates improved cancer treatment methods through fundamental and applied laboratory and clinical research across surgery, radiotherapy, chemotherapy, biological therapy, and supportive care modalities.

Abstract

Despite the recent success of cancer immunotherapy, less than 30% patients respond to immunotherapies. In the past, various innate immune-activating agents have been tested with disappointing clinical results. Recently, the cgas-sting pathway has been shown to activate dendritic cells and macrophages, resulting in stunning anti-tumor efficacy in various murine tumor models, thus generating intense interest. However, most sting agonists are based on cyclic dinucleotides that suffer from major limitations, including current limitations to the intratumoral route of injection, poor intracellular uptake, rapid in vivo degradation, and lack of a universal pathway for innate immune activation. Here, we propose to apply bioengineering principles to develop new sting-activating nanoparticles that can achieve potent systemic anti-tumor efficacy. We will evaluate the efficacy and safety of our proposed sting-activating nanoparticles in murine tumor models as well as in companion dogs with cancer. These in vivo studies are essential to assess systemic immune responses, nanoparticle distribution, efficacy, and toxicity. Such complex, whole-body processes cannot be reliably modeled in silico or in vitro, making animal studies necessary for evaluating therapeutic potential and supporting translation to human cancer immunotherapy. We anticipate that foundational technological advancements from these studies will lead to a new understanding of how to design and develop nanoparticlebased therapeutics.