Immunology researchers led by Dartmouth and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) have identified pathways through which cowpea mosaic virus, a plant virus that does not infect mammals, is recognized by the immune system. This discovery opens the door for a new biological drug for the treatment of cancer.
Research led by Steven Fiering, PhD, member of the Immunology and Cancer Immunotherapy Research Program at NCCC, previously showed that a plant virus that does not infect animals, cowpea mosaic 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 how an immune system can recognize a plant virus, and how and why this plant virus is exceptionally immuno-stimulating. In a new study, a collaboration with Dr. Nicole Steinmetz lab at University of California San Diego, the team identifies just how it is that CPMV is recognized by the immune system.
This plant virus is recognized by the immune system as a pathogen—any infectious agent that can cause disease. When tumors are injected with CPMV, molecules in the immune system send a warning signal of the invasion, which is heard by the “ears” of the immune system called toll-like receptors. The toll-like receptors then mobilize immune cells to attack the pathogen. “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 who is also a Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth.
During this stimulation process, a variety of immune system cells release immune stimulating molecules known as cytokines and attack the tumor. In a recent Biomaterials publication, the research team identifies the three toll-like receptors that recognize CPMV, and one cytokine in particular that has strong anti-tumor impact when used as an in situ vaccine.
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 this manner,” says Fiering.
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 Fiering and Nicole Steinmetz, PhD, of University of California San Diego, 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.
Early-phase trials of CPMV in situ vaccination in humans are planned to start in late 2021 or early 2022. Funding for this study provided by National Cancer Institute and Dartmouth’s and Dartmouth Hitchcock’s Norris Cotton Cancer Center.
LEBANON, NH (June 14, 2021) – Immunology researchers led by Dartmouth and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) have identified pathways through which cowpea mosaic virus, a plant virus that does not infect mammals, is recognized by the immune system. This discovery opens the door for a new biological drug for the treatment of cancer.
Research led by Steven Fiering, PhD, member of the Immunology and Cancer Immunotherapy Research Program at NCCC, previously showed that a plant virus that does not infect animals, cowpea mosaic 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 how an immune system can recognize a plant virus, and how and why this plant virus is exceptionally immuno-stimulating. In a new study, a collaboration with Dr. Nicole Steinmetz lab at University of California San Diego, the team identifies just how it is that CPMV is recognized by the immune system.
This plant virus is recognized by the immune system as a pathogen—any infectious agent that can cause disease. When tumors are injected with CPMV, molecules in the immune system send a warning signal of the invasion, which is heard by the “ears” of the immune system called toll-like receptors. The toll-like receptors then mobilize immune cells to attack the pathogen. “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 who is also a Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth.
During this stimulation process, a variety of immune system cells release immune stimulating molecules known as cytokines and attack the tumor. In a recent Biomaterials publication, the research team identifies the three toll-like receptors that recognize CPMV, and one cytokine in particular that has strong anti-tumor impact when used as an in situ vaccine.
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 this manner,” says Fiering.
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 Fiering and Nicole Steinmetz, PhD, of University of California San Diego, 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.
Early-phase trials of CPMV in situ vaccination in humans are planned to start in late 2021 or early 2022. Funding for this study provided by National Cancer Institute and Dartmouth’s and Dartmouth Hitchcock’s Norris Cotton Cancer Center.
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