To evaluate the accessibility of IL-11Ra as a target, the researchers intravenously administered small, virus-like particles called phages equipped with a peptide that mimics IL-11, the receptor's natural ligand. After 24 hours in circulation, the ligand-directed particles were taken up in the tumors but showed little or no accumulation in several control organs.
"Connecting therapeutic agents to this ligand-directed system might result in improved, targeted drugs," said co-senior author Renata Pasqualini, Ph.D., Professor of Medicine and Cancer Biology in the David H. Koch Center at M. D. Anderson.
"It is conceptually unexpected that a receptor would be over-expressed not only in metastatic tumors to bone but also in primary bone tumors; this is quite important because human osteosarcoma is a malignant tumor with very few targets at the protein level," said co-senior author Wadih Arap, M.D, Ph.D., also Professor of Medicine and Cancer Biology in the David H. Koch Center.
Immunohistochemical staining analysis of IL-11Ra expression in primary and metastatic human osteosarcoma samples provided further evidence of the potential value of IL-11Ra as a therapeutic target. All primary human osteosarcoma samples exhibited moderate-to high-intensity staining of tumor cells. More than half of tumor blood vessels also showed moderate-to-high-intensity staining. All pulmonary metastases were positive for IL-11Ra expression, while normal, control lung tissue was negative.
"This indicates that therapeutic targeting of IL-11Ra may yield anti-tumor, anti-metastasis and anti-angiogenesis effects in osteosarcoma," Lewis said.
Phase I trial of IL-11R for bone metastasis
The U.S. Food and Drug Administration recently issued "safe to proceed" status for an M. D. Anderson-sponsored investigational new drug based on
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center