Liposome Delivers Gene to Tumor Cells
Nonviral nanodelivery approach showing promise in clinical trials
Delivery of a tumor-suppressor gene to tumor cells using liposomes is showing promise in early human clinical trials, according to researchers. The therapy delivers a functioning p53 gene to tumor cells, which prompts the cells either to repair themselves or undergo programmed cell death, said Esther H. Chang, PhD.
Design of the nanoparticle, with gene payload inside a liposome and the targeting moiety on the outside.
The therapy delivers a functioning p53 gene to tumor cells, which prompts the cells either to repair themselves or undergo programmed cell death, said Esther H. Chang, PhD, a professor of oncology and otolaryngology at Georgetown University Medical Center, whose research team devised the therapy. Normal cells have two functioning copies of the p53 tumor-suppressor gene, but 95% of cancer cells have only one functioning copy, Dr. Chang explained.
"Based on extensive preclinical studies, we know that this approach can be equally effective even in tumors without the p53 mutation," she said. "Even if the p53 is wild-type, which is considered to be functional, still, this strategy will induce the tumors to undergo apoptosis."
Dr. Chang described the status of the phase 1 clinical trial at a recent meeting. (Chang EH. Materializing the potential of nanomedicine via a tumor-targeting nanodelivery platform. Paper presented at: Experimental Biology 2009; April 21, 2009; New Orleans).
Dr. Chang and her colleague, Kathleen Pirollo, PhD, a research associate professor at Georgetown, spoke to PFQ after the meeting.
"The payload of the therapy, the p53, is encapsulated in a liposome, and the targeting moiety is outside the liposome," Dr. Pirollo explained. "Its nano size allows it to penetrate deeply into the capillaries, using the enhanced permeability and retention effect to get into the area of the tumor cells, and then the targeting molecule binds it to the tumor cells."
She noted that the therapy targets metastases as well as the primary tumor.
"Preclinical studies showed that we are able to target and transfect even tiny little micro-mets in the lungs, the abdomen, the liver, wherever they are," Dr. Pirollo said.