Gene therapy makes multiple myeloma cells more sensitive to radiotherapy, researchers at the Mayo clinic say.
Copyright 2003, Biotech Week via NewsRx.com
"Multiple myeloma is a disseminated neoplasm of terminally differentiated plasma cells that is incurable with currently available therapies. Although the disease is radiosensitive, external beam radiation leads to significant toxicity due to sensitive end-organ damage," explained David Dingli and coauthors in the journal Blood.
The group has determined that lentiviral vectors facilitate the delivery of human sodium iodide symporter hNIS to multiple myeloma cells, making them more sensitive to radioactive molecules.
In preliminary analysis, researchers treated myeloma cell lines with self-inactivating (SIN) lentiviral vector encoded for enhanced green fluorescent protein to establish a baseline for transduction efficiency. Under the control of a minimal immunoglobulin promoter, 30-90% transduction efficiency was achieved with SIN vector.
Next, they encoded the vectors with hNIS gene and treated both cells and xenografts with the cancer-targeted therapy.
"Transduction of myeloma cells with the targeted vector coding for hNIS led to its expression by these cells allowing them to concentrate radioiodine up to 18-fold compared with controls," Dingli and colleagues reported.
The radioactive iodide was retained for at least 2 days in immunodeficient mice engrafted with human cancer. Total tumor eradiation and lack of recurrence was detectable for 5 months (Genetically targeted radiotherapy for multiple myeloma. Blood, 2003;102(2):489-496).
"Lentivectors can be transcriptionally targeted for myeloma cells and the use of hNIS as a therapeutic gene for myeloma in combination with 131I needs further exploration," study authors concluded.
The corresponding author for this study is Stephen J. Russell, Molecular Medicine Program, Mayo Clinic and Foundation, Rochester, MN,. USA.
Key points reported in this study include:
- Although external beam radiation destroys multiple myeloma, it can harm other organs of the body
- Gene therapy composed of lentiviral vector encoded for human sodium iodide symporter targets multiple myeloma cells
- The gene therapy sensitizes multiple myeloma cells to radioactive molecules that cause their destruction