Nanotechnology Platform Could Increase ICB Therapy Effectiveness

University of Arizona Health Sciences researchers recently completed a study that has the potential to improve cancer treatment for colorectal cancer and melanoma by using nanotechnology to deliver chemotherapy in a way that makes it more effective against aggressive tumors. The findings were published today in Nature Nanotechnology.

“To render a more effective ICB therapy, we have developed a nanotherapeutic platform that can switch the tumors from ‘immune-cold’ to ‘immune-hot,’” said lead researcher Jianqin Lu. “As a result, this nanotherapeutic platform was able to increase the effectiveness of the immune checkpoint blockade (ICB) therapy to eradicate a large portion of early-stage colorectal cancer tumors while concurrently activating the body’s memory immunity, preventing tumor recurrence.”   

The team attached camptothecin to sphingomyelin, a naturally occurring lipid found on the surface of cells. The combination of the two molecules into a nanovesicle called camptothesome stabilized camptothecin, improving its efficacy and diminishing systemic toxicities. The nanotech delivery method also improved the tumor uptake of the camptothesome in a rodent model, where it deeply penetrated the tumor with the efficient release of the chemotherapy.

The team then created a way to load an immune checkpoint inhibitor targeting one of the key checkpoints, indoleamine 2,3-dioxygenase (IDO1), inside of the camptothesomes. When combined with inhibitors targeting other immune checkpoints known as PD-L1 and PD-1, this nanotherapeutic strategy eliminated a significant portion of clinically difficult-to-treat late-stage metastatic colorectal cancer and melanoma tumors, paving the pathway for further studies.