January 29, 2021 // -- Scientists from the University of California and other institutions have developed a new DNA therapy that could help remove cancer stem cells from mouse bodies and help remove cancer stem cells from mouse bodies, according to a recent study published in the international journal Cell Stem Cell entitled "Selective antisense oligonucleotide resignion of human IRF4 prevents malignant myeloma regeneration via cell cycle.
Multiple myeloma is a blood cancer, and many patients with multiple myeloma eventually develop some tolerance to multiple therapies, in part because cancer stem cells drive diseased cells to constantly renew themselves, and if a treatment does not completely destroy these malignant stem cells, the cancer is likely to continue to relapse. In the
study, researchers developed a new targeted therapy for multiple myeloma, the expression of the silent gene IRF4, which allows myeloma stem cells and tumor cells to proliferate and survive, after several studies have shown that high levels of IRF4 are directly associated with a decline in overall survival in patients with multiple myeloma. In the
article, the researchers described how antisant oligonucleotides can be used to successfully inhibit and degrade the function of ILF4, a DNA specifically designed to bind encoded IRF4 genetic material, which, according to preclinical studies, is a research antisant developed by loris, known as ION251, that can help reduce the disease burden on patients and reduce the abundance of myeloma stem cells and increase survival in mice carrying human myeloma.
Photo Source: researchoutreach.org The results support a recently launched Phase I clinical trial to assess the safety and effectiveness of ION251 in the treatment of human multiple myeloma.
The University of California and loris Pharmaceuticals have been working together for years on the development of research antisal drugs, and several lonis antisal drugs have been commercially approved, such as the FDA-approved treatment SPINRAZA for spinal muscular dystrophy, and several other therapies are undergoing clinical trials.
The challenge for researchers working on myeloma today is that myeloma cells do not grow well in laboratory panties, and the best way to study the disease and detect new treatments is to transplant human myeloma cells into mice that lack an immune system (and do not reject human cells).
The researchers then tested the effects of ION251 in mice carrying myeloma, with significantly fewer myeloma cells in the body after 2-6 weeks of treatment than in untreated mice; None of the mice treated survived, while none of the untreated control mice survived; each treatment group or control group had 10 mice that received a daily dose of ION251 or the control group for one week followed by three doses of the drug every three weeks.
in experiments using human cells isolated from myeloma or health donor samples, the researchers used ION251 to remove myeloma stem cells without damaging healthy blood cells. 'These preclinical results are so striking that half of the microscope images we compared bone marrow samples between treated mice and untreated mice have been blank, and in the mice we treated, we couldn't find any myeloma cells that could be retained for research, which may make scientific research difficult, but hopeful for patients,' said Crews, a researcher at
In addition to being used for their own work, the therapy can improve the sensitivity of myeloma cells to standard cancer treatments, and the researchers have delved into the molecular mechanisms behind it and described the molecular effects of IRF4 inhibition, which shed light on how myeloma was first formed and how it works.
researchers say these principled validation studies will help develop an antisant oligonucleotide-mediated IRF4 inhibitory therapy that effectively prevents the recurrence of myeloma driven by drug-resistant cancer stem cells.
's Phase I clinical trial to assess the safety of ION251, initiated by Loris Pharmaceuticals, is working with cancer research centers at the University of California to recruit volunteers; multiple myeloma is the second most common blood cancer in the United States, with more than 32,000 new cases in 2020, according to the American Cancer Institute, with a five-year survival rate of just 53.9 percent.
() References: 1 Designer DNA therapeutic wipes out cancer stem cells, treats myeloma in miceby University of California - San Diego 2 Phoebe K. Mondala, Ashni A. Vora, Tianyuan Zhou, al. Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption, Cell Stem Cell (2021) doi：10.1016/j.stem.2020.12.017