UCLA researchers in the Department of Molecular and Medical Pharmacology have developed a cancer immunotherapy platform that uses lipid nanoparticle (LNP) delivery of modified RNA constructs to activate dendritic cells, enhance CD8+ T-cell priming, and drive potent anti-tumor immunity.
BACKGROUND: Effective cancer immunotherapy requires robust activation of dendritic cells (DCs) to support T-cell priming and durable immune responses. Current cancer vaccines frequently induce insufficient antigen presentation, limiting their therapeutic efficacy, particularly in tumors with heterogeneous or poorly characterized antigens. While mRNA vaccines have demonstrated clinical success, their activity is highly dependent on the immune stimulatory context provided to antigen-presenting cells. Thus, there is a pressing need for an adaptable RNA-based platform capable of activating multiple innate immune pathways, improving cross-presentation, and supporting both known and unknown tumor antigen targeting.
INNOVATION: Researchers at UCLA have developed a two-part RNA-based cancer immunotherapy by engineering both a stimulatory RNA and an antigen-encoding/therapeutic RNA to work together within lipid nanoparticles (LNPs). Researchers designed a novel RNA molecule that activates dendritic cells by triggering multiple innate immune pathways. They further paired this innate immune stimulant with modified mRNA encoding tumor antigens or immune-boosting cytokines. They optimized the route and schedule optimization and validated their effects in cell studies and in mouse tumor models. Collectively, the researchers demonstrated that combining immune stimulation with antigen or cytokine delivery within the same LNP platform generates stronger dendritic cell activation, more potent CD8+ T-cell responses, and meaningful anti-tumor activity compared to conventional mRNA vaccines.
POTENTIAL APPLICATIONS:
- Cancer immunotherapy platform
- Combination treatments with chemotherapy, etc.
- RNA-based immunomodulation for enhanced dendritic cell targeting
- Prophylactic or therapeutic vaccines against infectious diseases
ADVANTAGES:
- Flexible antigen selection
- Combination therapy
- Tailored DC activation and targeting
- Tunable modified RNA
- Route and schedule versatility
- Prime-boost strategies (efficacious via IM, IV, or IP administration)
- Durable immune response
- Broad immunological relevance
DEVELOPMENT-TO-DATE: UCLA researchers have developed a novel LNP-RNA based immunotherapy platform to drive potent immune responses. They have validated this platform in vitro and in vivo by showing strong dendritic cell and T cell activation with the combination immunotherapy in multiple mouse models.
Related Papers (from the inventors only):
Vadovics M, Zhao W, Daley EF, Lam K, Daly O, Rashid K, Lee HR, Schreiner P, Lundgreen KA, Gaudette BT, Shuvaev VV, Arguiri E, Muramatsu H, Sárközy A, Mdluli T, Xu J, Han X, De Luna N, Castaño D, Bettini E, Ábrahám E, Lipinszki Z, Carlucci G, Bansode AH, Nguyen K, Le TM, Luu T, Muzykantov VR, Bates P, Allman D, Mitchell MJ, Locci M, Radu CG, Heyes J, Pardi N. Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications. Nat Nanotechnol. 2025 Sep;20(9):1312-1322. doi: 10.1038/s41565-025-01958-5. Epub 2025 Jun 23. PubMed PMID: 40550975.
Keywords: Immunotherapy, RNA, vaccines, mRNA, RNA modifications, lipid nanoparticles, dendritic cell activation, PRR agonists, cancer vaccination, tumor-associated antigens, combination immunotherapy