Small plastic disks designed to prevent tumour growth can also destroy large tumours in mice, reports a new study. The bioengineered disks, which are implanted under the skin, have been shown previously in mice to work like a "concentrated vaccine" by redirecting the immune system to recognize and attack cancerous cells. A major challenge remains in developing treatments for patients with already existing tumours. In this new work, Omar Ali, David Mooney and colleagues demonstrate for the first time that a cancer vaccine can actually shrink solid tumours. This approach is a promising alternative to the costly, invasive, and extensive surgical procedures offered to cancer patients.
Once implanted into the skin the disks, which are 90% air, release cytokines; small proteins that rally immune-system messengers called dendritic cells. These cells crawl through the pores of the disks where they are exposed to substances called antigens, which activate the body’s immune response. The dendritic cells then report to nearby lymph nodes, where they activate the immune system's T cells to hunt down and kill cancer cells throughout the body. While current cancer vaccines prevent tumour growth in mice, most only activate one type of dendritic cell that is incapable of reducing tumour size.
In the study, the researchers manipulated the disk implant to activate several different types of dendritic and other immune cells, and found that 20-50 percent of mice vaccinated with these implants showed a complete regression of large, solid tumours--compared to untreated mice who eventually succumbed to cancer. Though it is not yet understood how the presence of different types of dendritic cells are linked to tumour shrinkage, these results are a step forward to designing a human cancer vaccine.
ecancer Managing Editor Prof Gordon McVie commented: "This is neat, and might be the way forward. The dendritic cells literature is clinically disappointing, and our team at IEO in Milan have been looking at combinations of dendritic cells and cytokines in melanoma. The bottleneck has been delivery, and this system may do the trick, as it allows multiple dendritic cell types to be combined with each other, and with cytokines. Transfer to the clinical trial will not be easy as each element of the system, and will need to be made to good laboratory practice etc. The disc will probably be treated like a medical device and will have to be shown to be safe, but it is practicable."
Article: Published in Science Translational Medicine: "In Situ Regulation of DC Subsets and T Cells Mediates tumour Regression in Mice," by O.A. Ali; D.J. Mooney at Harvard University in Cambridge, MA; O.A. Ali; D. Emerich at InCytu Inc. in Lincoln, RI; O.A. Ali; D.J. Mooney at Wyss Institute for Biologically Inspired Engineering in Cambridge, MA; G. Dranoff at Dana-Farber Cancer Institute in Boston, MA; G. Dranoff at Brigham and Women’s Hospital in Boston, MA; G. Dranoff at Harvard Medical School in Boston, MA.
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