Agents for Prevention of Cancer Cell Migration and Metastasis
Antibody-based fusion proteins that enable carrier-free, targeted delivery of RNA.
There are few treatments that directly target the metastatic spread of cancer cells from the primary tumor to surrounding tissues. CXCR4 is a chemokine receptor known to mediate cancer cell migration and metastasis in various cancer types through binding the endogenous cytokine CXCL12 (SDF-1) and blocking downstream signaling events.
This invention provides fusion proteins comprising an scFv and an RNA-binding protein that, when combined with RNA, self-assemble to produce a nanoplex that simultaneously acts as a targeting ligand, a receptor agonist/antagonist, and an RNA delivery vehicle. Demonstrated using an scFv that targets CXCR4, these nanoplexes not only inhibited cell migration and metastasis by interfering with CXCR4-CXCL12 (SDF-1) interactions, but they also further shifted tumor associated macrophages from an immunosuppressive, tumor-promoting M2 phenotype towards an immune-stimulating, tumor-suppressive M1 phenotype through co-delivery of an miRNA that exerts its effects through a distinct, intracellular target. These RNA-protein nanoplexes significantly inhibited cancer and immune cell migration (75 to 99%), robustly polarized macrophages to the tumor-suppressive M1 phenotype, and inhibited tumor growth in a mouse model of triple-negative breast cancer. These preliminary findings suggest these RNA-protein nanoplexes are promising adjuvants to currently approved therapies.
This technology provides carrier-free, targeted delivery of RNA, thus offering the potential for reduced toxicity and increased safety.
- RNA Therapeutics
US Provisional Patent Application 62/873,665 filed July 12, 2019.
In vivo demonstration.
Available for licensing or collaboration.
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