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December 23, 2015

Plant Virus Used as Cancer Immunotherapy Agent

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    Inhaled or injected into tumors of several types of cancer, the shell of cowpea mosaic virus with infectious components removed, in blue, turned on the immune system in mice to wipe out tumors and protect against metastases. [Nicole Steinmetz]

    The idea of using or injecting an oncolytic virus into a developing tumor, so that it could disrupt the cancer cells, while stimulating the immune system to attack the remaining tumor cells is almost as old as the field of oncology. However, the successful application of this technique, often called in situ vaccination, has remained challenging.

    Yet now, researchers from Case Western Reserve University and Dartmouth University have reported on how their results from the use of outer shell from a common plant virus—either inhaled into a lung tumor or injected into ovarian, colon or breast tumors—triggered an immune response to eliminate the cancer and provided systemic protection against metastases.

    The investigators utilized the hard outer coating of the cowpea mosaic virus (CPMV) as an adjuvant and the tumor itself like an antigen in a vaccine. Surprisingly, the researchers saw no detectable side effects or complications, which is often a common problem with traditional therapies and some immunotherapies.      

    "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," explained co-senior author Nicole Steinmetz, Ph.D., assistant professor of biomedical engineering at Case Western Reserve University School of Medicine.

    The findings from this study were published recently in Nature Nanotechnology through an article entitled “In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer.”

    "The particles are shockingly potent," noted co-senior author Steven Fiering, Ph.D., professor of microbiology and immunology at Dartmouth University’s Geisel School of Medicine. "They're easy to make and don't need to carry antigens, drugs, or other immunostimulatory agents on their surface or inside."

    The research teams were able to switch on the immune system in mice, using the CPMV approach, to attack B16F10 lung melanoma or skin melanoma, leaving the mice tumor-free. Moreover, when the treated mice were later injected with B16F10 skin melanoma, to re-challenge the cured mice, four out of the five mice remained cancer-free, and one had a slow-growing tumor.

    Additionally, the investigators showed that the viral nanoparticles were also effective against ovarian, breast, and colon tumor models. They observed that most of the tumors deteriorated from the center and collapsed while the systemic response prevented or attacked any metastatic disease.

    "You get benefits against disease you don't even know is there yet," Dr. Fiering remarked. "Because everything we do is local, the side effects are limited." Regardless of the strength and extent of the immune response, the researchers consistently noted that no toxicity was found.

    The researcher groups are now committed to understanding how the viral shell stimulates the immune system so vigorously. To their surprise, the scientists noticed that unlike most adjuvants, the CPMV shell stimulates neutrophils in the immune response. Why this occurs is currently still a mystery to the researchers. 

    “It's not cytotoxic, there's no RNA involved or lipopolysaccharides that may be used as adjuvants, and it's not simply an irritant," Dr. Steinmetz said. "We see a specific immune response."

    The authors were excited about their findings and are looking to test their novel therapy in more animal models. If the viral shell continues to prove effective, the researchers believe it could eventually be used in combination with other therapies tailored to individual patients.

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