Researchers at the University of Arizona R. Ken Coit School of Pharmacy have developed a new strategy that helps the immune system more effectively recognize and attack lung cancer tumors. By packaging chemotherapy drugs and RNA molecules into small lipid carriers, the researchers boosted the immune response, slowed tumor growth, and increased the effectiveness of immunotherapy.
The survey results are nature communicationsdescribe a nanotechnology-based platform that combines the chemotherapy drug paclitaxel with gene-silencing molecules known as siRNAs. Lipid packaging improves the delivery of both therapies to lung tumor cells.
This approach enhances a process called immunogenic cell death (ICD). ICD is a form of cancer cell death that alerts the immune system to the presence of a tumor. Researchers increasingly see ICDs as a promising way to help the body recognize, attack and remember cancer cells.
Jianqin Lu, John A., and Frances P. Ware, endowed associate professor of pharmacy in the university’s School of Pharmacy and a member of the university’s Comprehensive Cancer Center, led the study.
Despite the great potential of ICD-based immunotherapy, its therapeutic applications remain underutilized. Knowing that paclitaxel can induce ICD, researchers improved the delivery of the drug to tumors by attaching fat molecules called sphingolipids to form fat bubbles, or nanovesicles. More drugs can be delivered to the tumor site. ”
Jianqin Lu, John A., Frances P. Ware Endowed Associate Professor of Pharmacy, College of Pharmacy
When the drug kills cancer cells, a protein called calreticulin (CRT) moves to the surface of the dying cells, producing what researchers describe as an “eat me” signal that attracts immune cells. CRT acts as a beacon for cells called phagocytes that engulf dying tumor cells and help initiate an ICD response.
Some tumors circumvent this response by using a molecule called STC1 that prevents CRT from reaching the cell surface. As a result, the immune response is weakened and the activity of cell-killing T cells is reduced.
To counter this effect, the researchers used an siRNA molecule called siSTC1 and co-delivered it with paclitaxel to suppress the activity of the STC1 gene.
The research team tested this strategy in two cancer cell lines: Lewis lung cancer cells, which have high STC1 gene expression, and MC38 colon cancer cells, which have low STC1 expression of these genes. They found that the combination of this drug and siRNA that silenced the STC1 gene was much more effective against lung cancer cells than against MC38 cells.
“If we trigger an ICD immune response, there should be no tumor development or delay in tumor development,” Lu said.
Using a mouse model of lung cancer, Lu et al. found that the combination of SCT1 siRNA and paclitaxel could eradicate three out of five tumors, and in some cases four out of five tumors, depending on the type of cancer.
Researchers also found that the siSTC1-paclitaxel package made tumors more sensitive to PD-1 blockade therapy, a type of cancer immunotherapy that allows the immune system to better recognize and destroy cancer cells.
“You’re really changing the tumor microenvironment,” Lu said. “The combination of paclitaxel and siSTC1 enhances PD-1 inhibition therapy and cancer immunotherapy, which is why these types of processes have an impact.”
Lu said the platform could be used to treat many cancer types with high STC1 expression, including non-small cell lung cancer, some colon cancers, breast cancer, liver cancer, and ovarian cancer.
The team hopes to work with clinical oncologists and eventually advance the platform in a phase 1 clinical trial.
Other co-authors from the College of Pharmacy include Wenpan Li, researcher/scientist III; Zhiren Wang, former postdoctoral fellow. Mengwen Li, PhD student in Pharmacy. Yanhao Jiang, PhD student in Pharmacy. Shuang Wu, PhD student in Pharmacy. Leila Cordova, master’s student in pharmacy. Kim Min-hyuk, former undergraduate student researcher.
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Reference magazines:
Lee, W. others. (2026). Promoting immunogenic tumor cell death through nanotherapeutic targeting of the stanniocalcin-1 phagocytic checkpoint to enhance cancer immunotherapy. nature communications. DOI: 10.1038/s41467-026-72526-1. https://www.nature.com/articles/s41467-026-72526-1
