PHILADELPHIAIntranasal delivery of an adenoviral vector
containing the murine interleukin-12 (IL-12) gene has been shown to
inhibit osteosarcoma lung metastases in mice. IL-12 is a molecule
that activates the immune system and has recently been shown to have
antiangiogenic activity. Our hypothesis is that IL-12
interfered with tumor angiogenesis, Laura L. Worth, MD, PhD,
said at the annual meeting of the American Association for Cancer
Dr. Worth, junior faculty associate, M.D. Anderson Cancer Center, and
her colleagues found that the mice that received the IL-12 treatment
had a significant reduction in the size and number of tumors that had
spread to the lungs: a median of 1.5 tumors vs 32 for controls.
SAOS-LM6 human osteosarcoma cells were produced by repetitive cycling
through the mouse lung. The system of adenoviral-mediated IL-12 gene
transfer was developed by Ling Chen, PhD.
The affected mice received a droplet containing either the IL-12 gene
or another gene used as a control in the nose twice a week for 4
weeks. The data indicated that intranasal IL-12 gene therapy is
feasible and effective, Dr. Worth said.
Since IL-12 is species specific, the researchers concluded that the
IL-12 produced following inhalation therapy affected the mouse
microenvironment rather than the human tumor cells. Additional
studies are underway to confirm this, she said. We believe
that, by decreasing new blood vessel formation and depriving the
tumors of necessary nutrients, this nasal therapy can effectively
contain lung metastases, Dr. Worth concluded.