Fingernail-sized implant successfully eliminates tumors in mammals
By Darren Quick
November 26, 2009
In a world first, scientists have successfully eliminated tumors in mammals using a cancer vaccine carried into the body on a fingernail-sized implant. The new approach uses plastic disks impregnated with tumor-specific antigens and implanted under the skin to reprogram the mammalian immune system to attack tumors.
Most cancer cells easily skirt the immune system, which operates by recognizing and attacking invaders from outside the body. The approach developed by bioengineers and immunologists at Harvard University redirects the immune system to target tumors, and appears both more effective and less cumbersome than other cancer vaccines currently in clinical trials.
Conventional cancer vaccinations remove immune cells from the body, reprogram them to attack malignant tissues, and return them to the body. However, more than 90 percent of reinjected cells die before having any effect in experiments.
The slender implants developed by the group measure 8.5 millimeters in diameter and are made of an FDA-approved biodegradable polymer. Ninety percent air, the disks are highly permeable to immune cells and release cytokines, powerful recruiters of immune-system messengers called dendritic cells.
These cells enter an implant’s pores, where they are exposed to antigens specific to the type of tumor being targeted. The dendritic cells then report to nearby lymph nodes, where they direct the immune system’s T cells to hunt down and kill tumor cells.
“Inserted anywhere under the skin - much like the implantable contraceptives that can be placed in a woman’s arm - the implants activate an immune response that destroys tumor cells,” said David J. Mooney the Robert P. Pinkas Family Professor of Bioengineering in Harvard’s School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering who led the research.
The technique may have powerful advantages over surgery and chemotherapy, and may also be useful in combination with existing therapies. It only targets tumor cells, avoiding collateral damage elsewhere in the body. And, much as an immune response to a bacterium or virus generates long-term resistance, researchers anticipate that cancer vaccines will generate permanent and body-wide resistance against cancerous cells, providing durable protection against relapse.
Mooney said the new approach’s strength lies in its ability to simultaneously regulate the two arms of the human immune system: one that destroys foreign material, and one that protects tissue native to the human body. The implant-based vaccine recruits several types of dendritic cells that direct destructive immune responses, creating an especially potent anti-tumor response.
The Harvard research groups work is detailed in the paper, “In Situ Regulation of DC Subsets and T Cells Mediates Tumor Regression in Mice”, which appears in the journal Science Translational Medicine.