Credit: Daniel E. Sabath
A novel compound can prevent metastasis in mouse models of multiple myeloma (MM), according to research published in Cell Reports.
Investigators discovered that this compound, olaptesed pegol, can inhibit stromal cell-derived factor-1 (SDF-1), which attracts certain cells to new locations within the bone marrow.
By blocking the activity of SDF-1, olaptesed pegol renders the bone marrow uninviting to MM cells and prevents metastasis.
“Metastasis remains one of the most formidable complications we face as cancer researchers and physicians,” said study author Irene Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.
“Improvements in the treatment of metastatic cancers have, for the most part, not been nearly as dramatic as in primary disease.”
Dr Ghobrial and her colleagues studied MM because it is metastatic by nature. Myeloma cells originate in the bone marrow, depart for the bloodstream, and eventually return to the bones, where they form numerous colonies.
The team found that mice with advanced stages of MM had higher levels of SDF-1 at sites in the bones where metastasis had occurred.
“We reasoned that by neutralizing SDF-1, we could change the bone marrow environment to make it less receptive for multiple myeloma cells, reduce myeloma cells’ affinity for the marrow, and thereby inhibit the progression of the disease,” said Aldo Roccaro, MD, PhD, also of Dana-Farber.
Working with the German biotechnology company NOXXON Pharma, the investigators tested olaptesed pegol (a PEGylated mirror-image L-oligonucleotide), which binds to SDF-1.
The team found that olaptesed pegol modulates bone marrow niches and prevents MM cells from homing and engrafting to bone.
This slowed disease progression and prolonged survival in the animals, both compared to control mice and mice treated with AMD3100.
The investigators said it isn’t completely clear what becomes of the blood-borne MM cells that are prevented from metastasizing.
“We know that myeloma cells can’t survive for long if they’re circulating in the blood and can’t adhere to other tissue,” Dr Ghobrial said. “We saw no evidence that they had metastasized and begun to grow in other tissue either.”
“Our findings clearly document a therapeutic effect of olaptesed pegol in a mouse model of advanced myeloma. It is now being tested in a clinical trial of multiple myeloma patients, with more trials to come.”
