First cancer vaccine to eliminate tumors in mice

A cancer vaccine carried into the body on a carefully engineered,
fingernail-sized implant is the first to successfully eliminate tumors
in mammals, a team of Harvard bioengineers and biologists report today in the journal
Science Translational Medicine.

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. The journal article describes the use of such
implants to eradicate melanoma tumors in mice.

“This work shows the power of applying engineering approaches to immunology,” said David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering in Harvard’s School of Engineering and Applied Sciences and a member of the faculty of the Wyss Institute for Biologically Inspired Engineering. “By marrying engineering and immunology through this collaboration with Harvard Medical School associate professor Glenn Dranoff, at the Dana-Farber Cancer Institute, we’ve taken a major step toward the design of effective cancer vaccines.”

Most cancer cells easily skirt the immune system, which operates by
recognizing and attacking invaders from outside the body. The approach
developed by Mooney’s group 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 Mooney’s 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,” Mooney said.

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 bodywide 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.

“This approach is able to simultaneously upregulate the destructive
immune response to the tumor while downregulating the arm of the immune
system that leads to tolerance,” Mooney said. “In cancer, this latter
arm is typically a limiting feature of immunotherapies, since it can
extinguish vaccine activity and afford tumors a degree of protection.”

Mooney’s co-authors additional co-authors include Omar A. Ali
of Harvard’s School of Engineering and Applied Sciences, the Wyss
Institute for Biologically Inspired Engineering, and InCytu, Inc. and
Dwaine Emerich of InCytu Inc. Their work was
supported by the National Institutes of Health, Harvard, and
InCytu Inc.