In a Tucson laboratory, a research team has found a promising new way to help the immune system recognize and destroy lung cancer tumors — and early results suggest they may be onto something significant. Scientists at the University of Arizona College of Pharmacy, working with researchers from Zhejiang University and the University of Macau, have developed a tiny lipid-based package that delivers two therapies directly to tumors: a chemotherapy drug called paclitaxel and a gene-silencing molecule known as siRNA. In experiments with mice, this combination erased tumors in three out of five test subjects — and in some cancer types, four out of five.
The approach, published in Nature Communications, works by enhancing a natural process called immunogenic cell death, or ICD. When cancer cells die in a particular way, they send out signals that alert the immune system to their presence — essentially a beacon that tells the body something dangerous is there. Paclitaxel can trigger this process, but tumors often resist it by producing a molecule called STC1, which blocks the signal. The team solved this problem by adding siRNA that silences the STC1 gene, allowing the immune alarm to sound unimpeded.
"If you trigger an ICD immune response, there should be no tumor development or delayed tumor development," said Jianqin Lu, the John A. and Frances P. Ware Endowed Associate Professor of Pharmaceutical Sciences who led the research. Lu and her colleagues attach a fatty molecule called a sphingolipid to form what she describes as a "fatty bubble" that can slip more easily into tumor cells.
Once the treatment breaks through, a protein called calreticulin rises to the surface of dying cells — an "eat me" signal that attracts immune cells called phagocytes. These cells engulf the dying tumor fragments and help activate T-cells that can recognize and attack remaining cancer cells throughout the body. The team also found that their approach made tumors far more responsive to PD-1 blockade therapy, a common immunotherapy that helps the immune system better target cancer.
"You're really changing the tumor microenvironment," Lu said. "The paclitaxel-siSTC1 combination potentiates the PD-1 blockade therapy and the cancer immunotherapy."
The research focused on lung cancer cells with high STC1 expression, but the platform could potentially be adapted to treat a range of cancers including certain colon, breast, liver, and ovarian cancers — all types where STC1 levels are elevated. The team is now seeking to partner with clinical oncologists with the goal of eventually moving the treatment into a phase 1 clinical trial.
The findings represent a step toward making immunogenic cell death live up to its therapeutic promise, an area Lu says has remained "underused" despite its potential. With further development, this nanotechnology approach could give the body's own defenses a stronger starting position in the fight against cancer.