Mantle cell lymphoma in the bone marrow may appear similar to other lymphoproliferative disorders. Immunohistochemical staining for cyclin D1 is helpful in diagnosing this entity.
With a median survival rate of 5-7 yrs, Mantle Cell Lymphoma (MCL) is considered the most aggressive known blood cancer – and available therapies are scarce. 3000 Americans are diagnosed with MCL every year. Tel Aviv University researchers offer tangible hope of curing the currently incurable blood cancer – and others like it. The revolutionary system was found to successfully halt the proliferation of a cancer-related protein in WBCs in both animal models and samples taken from MCL patients.
“MCL has a genetic hallmark,” said Dr. Peer. “In 85% 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 2 years ago in Dr. Peer’s lab 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.
They 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 Dr. Peer. “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 RNA interference we have developed targets the faulty Cyclin D1 within the cancerous cells. And when the cells are inhibited from proliferating, they sense they are being targeted and begin to die off.”
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. “This research makes a definite contribution to the revolution of personalized medicine, whereby you tailor the drug based on the genetic profile of patient,” said Dr. Peer. “In this case, MCL is a disease with a specific genetic hallmark, so you can sequence the patient to identify the mutation(s), and design RNA blockers to be placed inside a nanovehicle.
https://www.aftau.org/weblog-medicine–health?=&storyid4704=2241&ncs4704=3
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