Researchers discover how cowpea mosaic plant virus activates immune system against cancer

LEBANON, NH – Previous work by a team of researchers led by Steven N. Fiering, PhD, Immunology and Cancer Immunotherapy Investigator at Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center and Nicole Steinmetz, PhD, Jacobs School of Engineering and Moores Cancer Center, University of California San Diego, showed that a plant virus that does not infect mammals, the cowpea mosaic plant virus (CPMV), when injected into cancer tumors, strongly stimulated the immune system to attack and often eliminate the tumor. However, very little was understood about immune recognition of plant viruses and how and why CPMV is exceptionally immunostimulatory. In a new study, the team identifies how CPMV is recognized by the immune system, opening the door for CPMV to be pursued as a new biologic drug for cancer treatment.

CPMV is recognized by the immune system as a pathogen — any infectious agent that can cause disease — through a family of receptors on immune cells called toll-like receptors. Toll-like receptors recognize molecules that signal the invasion of a pathogen and send a warning signal to the immune cells to mobilize to attack the pathogen. When tumors are injected with CPMV, the immune system activates and attacks the tumors through this pathogen pattern recognition. “The recognition of CPMV by toll-like receptors illustrates how these receptors are quite flexible and recognize many more molecular patterns than immunologists previously knew,” says Fiering.

During the immune stimulation process, the immune cells release proteins that signal and activate other immune cells, known as cytokines. The team’s study, “Cowpea mosaic virus boosts antitumor immunity through recognition by multiple MYD88-dependent toll-like receptors,” newly published in Biomaterials, identifies the three toll-like receptors that recognize CPMV. The article also highlights the importance of a particular cytokine, “interferon-alpha”, for strong anti-tumor impact when used as an in situ vaccine to treat cancer.

In situ vaccination, in which tumors are directly treated with immune-stimulating reagents, has powerful potential to improve cancer immunotherapy in a safe and inexpensive manner. “In situ vaccination has already made a contribution to cancer treatment. CPMV is an excellent reagent that could soon be used to help patients in the same way,” says Fiering. “The in situ vaccination treatment of a tumor by CPMV can stimulate the immune system to also attack distant metastatic tumors that have not been treated.”

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The commercial development of CPMV as a biologic drug for the treatment of cancer in the form of in situ vaccination is being conducted by Mosaic ImmunoEngineering Inc., a biotech company co-founded by Steinmetz and Fiering with a team of scientists and entrepreneurs. The company has licensed the rights to this technology and is actively striving to bring it to the clinic for the direct benefit of patients.

Phase I trials of in situ vaccination with CPMV in humans are planned for late 2021 or early 2022.

Steven N. Fiering, PhD, is Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth, and a member of the Immunology and Cancer Immunotherapy Research Program at the Norris Cotton Cancer Center of Dartmouth and Dartmouth-Hitchcock. His research interests include developing clinically useful in situ vaccination approaches to generate therapeutic anti-tumor immunity.

About Norris Cotton Cancer Center

Located on the Dartmouth-Hitchcock Medical Center (DHMC) campus in Lebanon, NH, Norris Cotton Cancer Center combines advanced cancer research at Dartmouth College’s Geisel School of Medicine in Hanover, NH with the highest level of quality, innovative, personalized, and compassionate patient-centered cancer care at DHMC, as well as at regional, multidisciplinary sites and partner hospitals in NH and VT. NCCC is one of only 51 centers nationwide to have earned the prestigious National Cancer Institute’s “Comprehensive Cancer Center” designation, the result of an outstanding partnership between DHMC, New Hampshire’s only academic medical center, and Dartmouth College. Entering its fifth decade, NCCC remains committed to excellence, outreach and education, striving to prevent and cure cancer, improve survival rates, and advance cancer health through cutting-edge interdisciplinary research. Each year, the NCCC schedules 61,000 appointments with nearly 4,000 newly diagnosed patients, and currently offers its patients more than 100 active clinical trials.

About Dartmouth-Hitchcock Health

Dartmouth-Hitchcock Health (D-HH), New Hampshire’s only academic health system and the state’s largest private employer, serves a population of 1.9 million people in northern New England. DH provides access to more than 2,000 healthcare providers in nearly every field of medicine and delivers care at its flagship hospital, Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH. DHMC was again named the #1 hospital in New Hampshire in 2020 by US News & World Report, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock also includes the Norris Cotton Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation; the children’s hospital at Dartmouth-Hitchcock, the state’s only children’s hospital; affiliated affiliated hospitals in Lebanon, Keene and New London, NH, and Windsor, VT, and visiting nurse and hospice for Vermont and New Hampshire; and 24 Dartmouth-Hitchcock clinics providing outpatient services in New Hampshire and Vermont. The DH System educates nearly 400 residents and fellows annually and conducts world-class research, in partnership with the Geisel School of Medicine in Dartmouth and the White River Junction VA Medical Center in White River Junction, VT.

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