Immunology researchers led by Dartmouth and Dartmouth-Hitchcock’s Norris Cotton Cancer Center discover how the cowpea mosaic plant virus is recognized by and strongly stimulates the immune system to attack and often eliminate cancerous tumors
Previous work by a team of researchers led by Steven N. Fiering, PhD, Immunology and Cancer Immunotherapy researcher 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, cowpea mosaic plant virus (CPMV), when injected into cancerous 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 immuno-stimulating. In a new study, the team identifies just how CPMV is recognized by the immune system, opening the door for CPMV to be pursued as a new biological drug for treatment of cancer.
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 by way of 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 stimulates 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 paper 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, have powerful potential to improve cancer immunotherapy in a safe and inexpensive manner. “In situ vaccination has made contributions already to cancer treatment. CPMV is an excellent reagent that may soon be used to help patients in the same manner,” 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.”
Commercial development of CPMV as a biological drug for the treatment of cancer in the form of in situ vaccination is in progress 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 pursuing bringing it to the clinic for the direct benefit of patients.
Phase I trials of CPMV in situ vaccination in humans are planned to start in late 2021 or early 2022.
Steven N. Fiering, PhD, is a 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 Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center. His research interests include developing clinically useful in situ vaccination approaches to generate therapeutic anti-tumor immunity.
Featured image: Though it does not infect mammals, the Cowpea mosaic plant virus is recognized by and strongly stimulates the immune system to attack and often eliminate cancerous tumors. © UCSD
Reference: Chenkai Mao, Veronique Beiss, Jennifer Fields, Nicole F. Steinmetz, Steven Fiering, Cowpea mosaic virus stimulates antitumor immunity through recognition by multiple MYD88-dependent toll-like receptors, Biomaterials, 2021, 120914, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2021.120914. (https://www.sciencedirect.com/science/article/pii/S0142961221002702)
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