With a median survival rate of just five to seven years, Mantle Cell Lymphoma (MCL) is considered the most aggressive known blood cancer -- and available therapies are scarce.
In 85 percent of cases, the characteristic that defines this aggressive and prototypic B-cell lymphoma is the heightened activity of the gene CCND1, which leads to the extreme overexpression -- a 3,000- to 15,000-fold increase -- of Cyclin D1, a protein that controls the proliferation of cells. Downregulation of Cyclin D1 using siRNAs is a potential therapeutic approach to this malignancy.
The research validates a novel strategy developed two years ago that involved small interfering RNAs (siRNAs). The radical new delivery system harnesses nanoparticles coated with "GPS" antibodies that navigate toward the location of the cancerous cells, where they then offload Cyclin D1-blockers in the form of siRNAs.
For the purpose of the research, the scientists designed lipid-based nanoparticles (LNPs) coated with anti-CD38 monoclonal antibodies that were taken up by human MCL cells in the bone marrow of affected mice. When loaded with siRNAs against Cyclin D1, the targeting LNPs induced gene silencing in MCL cells and prolonged the survival of tumor-bearing mice with no observed adverse effects.
In MCL, Cyclin D1 is the exclusive cause of the over-production of B Lymphocytes, the cells responsible for generating antibodies," said the author. "This makes the protein a perfect target for RNA therapy by siRNAs. Normal, healthy cells don't express the gene, so therapies that destroy the gene will only attack cancer cells.
The new research highlights the therapeutic potential of Cyclin D1 therapy in MCL and presents a novel RNA delivery system that opens new therapeutic opportunities for treating MCL and other similar B-cell malignancies.