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.Steven Fiering, PhD
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.
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 across northern New England. D-HH provides access to more than 2,000 providers in almost every area of medicine, delivering care at its flagship hospital, Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH. DHMC was named again in 2020 as the #1 hospital in New Hampshire by U.S. News & World Report, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock Health includes the Norris Cotton Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation Children's Hospital at Dartmouth-Hitchcock, the state’s only children’s hospital; member 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 that provide ambulatory services across New Hampshire and Vermont. The D-HH system trains nearly 400 residents and fellows annually, and performs world-class research, in partnership with the Geisel School of Medicine at Dartmouth and the White River Junction VA Medical Center in White River Junction, VT.
About the Geisel School of Medicine at Dartmouth
The Geisel School of Medicine at Dartmouth, founded in 1797, strives to improve the lives of the communities we serve through excellence in learning, discovery, and healing. The nation's fourth-oldest medical school, the Geisel School of Medicine has been home to many firsts in medical education, research and practice, including the discovery of the mechanism for how light resets biological clocks, creating the first multispecialty intensive care unit, the first comprehensive examination of U.S. health care cost variations (The Dartmouth Atlas), and the first Center for Health Care Delivery Science, which launched in 2010. As one of America's top medical schools, Dartmouth's Geisel School of Medicine is committed to training new generations of physician leaders who will help solve our most vexing challenges in health care.
About Norris Cotton Cancer Center
Norris Cotton Cancer Center, located on the campus of Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH, combines advanced cancer research at Dartmouth College’s Geisel School of Medicine in Hanover, NH with the highest level of high-quality, innovative, personalized, and compassionate patient-centered cancer care at DHMC, as well as at regional, multi-disciplinary locations and partner hospitals throughout NH and VT. NCCC is one of only 52 centers nationwide to earn the National Cancer Institute’s prestigious “Comprehensive Cancer Center” designation, the result of an outstanding collaboration between DHMC, New Hampshire’s only academic medical center, and Dartmouth College. Now entering its fifth decade, NCCC remains committed to excellence, outreach and education, and strives to prevent and cure cancer, enhance survivorship and to promote cancer health equity through its pioneering interdisciplinary research. Each year the NCCC schedules 61,000 appointments seeing nearly 4,000 newly diagnosed patients, and currently offers its patients more than 100 active clinical trials.