Chemoimmunotherapy is a promising technology in the fight against cancer. Researchers at the University of Michigan Rogel Cancer Center have designed a new delivery system – a drug hidden in a nanodisc – to increase the number of patients who can be treated successfully with cancer immunotherapy drugs.
A nanodisc is made of a synthetic version of high density lipoprotein (HDL), also known as “good cholesterol.” Researchers attached doxorubicin, a widely used chemotherapy drug, to the nanodisc.
“When we attached the chemotherapy drug to the synthetic HDL, we saw significant improved circulation half-life, improved delivery to the tumor cells and a better accumulation of the drug in the tumor cells,” says study co-senior author Anna Schwendeman, Ph.D., assistant professor of pharmaceutical science at the U-M College of Pharmacy.
“The most surprising part of the research was that when tumor cells were killed, it triggered anti-tumor immunity,” Moon says. The immune system was empowered to recognize and attack tumor cells.
There were no overt side effects to the new delivery system. And interestingly, the researchers discovered another unexpected benefit: less impact on the heart.
“Often when patients receive doxorubicin, they have cardiotoxicity because heart muscle cells accumulate the drug. But we found that by delivering doxorubicin on the synthetic HDL nanodisc, we saw better accumulation of the drug in the tumor and we didn’t detect any cardiotoxicity,” Schwendeman says.
“HDL is known to have benefits for the heart. That may have contributed to the absence of cardiotoxicity,” she adds, noting that more research is needed to confirm that speculation.
Phase I trials have been conducted for the synthetic HDL nanodisk alone. The next step is to to test the combined therapy on humans in clinical trials.