Source: University of Michigan
Summary: Researchers designed new delivery system, a drug hidden in a nanodisc to increase the number of patients who can be treated successfully with cancer immunotherapy drugs.
To determine if cells are harmful to the body and need to be attacked, the immune system uses certain molecules called checkpoints. But some cancer cells avoid an immune system attack by producing proteins that trick the checkpoints. Checkpoint blockers were designed to allow immune cells to kill cancer cells. Researchers from the University of Michigan designed new delivery system, a drug hidden in a nanodisc to increase the number of patients who can be treated successfully with cancer immunotherapy drugs. The nanodisc is made of a synthetic version of high-density lipoprotein (HDL), also known as “good cholesterol.” Then researchers attached doxorubicin, a widely used chemotherapy drug, to the nanodisc. The study findings were published in the journal Science Advances.
In multiple mouse tumor models of colon cancer, researchers found up to 85% of the tumors were completely eliminated when combining the nanodisc-delivered chemotherapy with immune checkpoint blockers, a common immunotherapy treatment. In a more challenging model of cancer, one that metastasized to the liver, the treatment also showed an excellent response rate of 88%. By using the synthetic HDL, which mimics natural HDL in the body, the researchers were able to hide the chemotherapy from the immune system. The most surprising part of the research was that when tumor cells were killed, it triggered anti-tumour immunity. There were no overt side effects to the new delivery system. And interestingly, the researchers discovered another unexpected benefit: less impact on the heart.
Assoc. Prof. James J. Moon said, “The combination of chemoimmunotherapy on a synthetic HDL nanodisc could have a big positive impact for cancer patients. Our results demonstrating their efficacy in multiple tumor models suggest that our strategy may have wide applications in multiple cancer types.”
More Information: Rui Kuai et al, “Elimination of established tumors with nanodisc-based combination chemoimmunotherapy” Science Advances (2018). DOI: 10.1126/sciadv.aao1736