Simple shell of plant virus sparks immune response against cancer

The shells of a common plant virus, inhaled into a lung tumor or injected into ovarian, colon or breast tumors, not only triggered the immune system in mice to wipe out the tumors, but provided systemic protection against metastases, researchers from Case Western Reserve University and Dartmouth University report.

The scientists tested a 100-year-old idea called in-situ vaccination. The idea is to put something inside a tumor and disrupt the environment that suppresses the immune system, thus allowing the natural defense system to attack the malignancy.

That something - the hard coating of cowpea mosaic virus - caused no detectible side effects, which are a common problem with traditional therapies and some immunotherapies.

The team's research is published in the journal Nature Nanotechnology.

"The cowpea virus-based nanoparticles act like a switch that turns on the immune system to recognize and fight against the tumor - as well as to remember it," said Nicole Steinmetz, an assistant professor of biomedical engineering at Case Western Reserve, appointed by the Case Western Reserve School of Medicine.

"The particles are shockingly potent," said Steven Fiering, professor of microbiology and immunology at Dartmouth's Geisel School of Medicine. "They're easy to make and don't need to carry antigens, drugs or other immunostimmulatory agents on their surface or inside."

The professors studied the nanoparticles with Dartmouth's Pat Lizotte, a molecular and cellular biology PhD student; Mee Rie Sheen, a postdoctoral fellow; and Pakdee Rojanasopondist, an undergraduate student; and Case Western Reserve's Amy Wen, a biomedical engineering PhD student.

Taking another shot

The immune system's ability to detect and destroy abnormal cells is thought to prevent many cancers, according to the National Cancer Institute. But when tumors start to develop, they can shut down the system, allowing tumors to grow and spread.

To restart immune defenses, the scientists used the tumor itself as if it were the antigen in a vaccine - that is, the target for antibodies produced by the immune system.

The cowpea virus shell, with its infectious components removed, acts as the adjuvant - a substance that triggers and may enhance or prolong antigen-specific immune responses.

The process and results

The researchers first switched on the immune system in mice to attack B16F10 lung melanoma or skin melanoma, leaving the mice tumor-free. When the treated mice were later injected with B16F10 skin melanoma (to re-challenge the cured mice), four out of five mice were soon cancer free and one had a slow-growing tumor.