Treating deadly mammary cancer with a novel plant virus-based immunotherapy

LEBANON, NH –  Dogs, like humans, are affected by cancer. The ability to treat spontaneous tumors in veterinary patients provides a unique opportunity to identify therapies that could also benefit human cancer patients. One of these diseases, inflammatory breast cancer (IBC) is a rare but deadly type of human breast cancer. Female dogs can develop a similar inflammatory mammary cancer (IMC) that occurs in dogs outside of the U.S., due to lower rates of spaying young female dogs. Both IBC and IMC lack effective therapies, and the aggressiveness of this disease generally precludes surgery.

Now, researchers from Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) are leading the investigation of potential immunotherapeutic treatment for human IBC, by evaluating efficacy, safety, and clinical benefit of cowpea mosaic virus (CPMV) nanoparticle injections into tumors of companion dogs with IMC. The study, “Neoadjuvant in situ vaccination with cowpea mosaic virus as a novel therapy against canine inflammatory mammary cancer,” is newly published in Journal for ImmunoTherapy of Cancer. This collaboration was coordinated by Hugo Arias-Pulido, PhD, senior scientist in the Fiering laboratory, and Steven N. Fiering, PhD, Member of NCCC’s Immunology and Cancer Immunotherapy Research Program. The study involved veterinarians at Complutense University of Madrid, Spain and researchers from University of California, San Diego led by Nicole Steinmetz, PhD, and University of Zurich, Switzerland.

Intra-tumoral injection of CPMV immunotherapy was the only treatment provided to five female companion dogs affected with IMC. The therapy generated potent local and systemic anti-tumor immune responses, was safe without any apparent adverse effects, and resulted in better quality of life and significantly extended survival of the treated dogs when compared to untreated dogs. While surgery is not an expected option with this very aggressive cancer, CPMV treatment stimulated anti-tumor immune responses that reduced injected tumors sufficiently to enable surgery in two of the dogs.

“This is exciting because the tumor reduction and improvement in survival has not been observed in IMC patients with a single monotherapy as we observed with the CPMV nanoparticles,” says Arias-Pulido. “The potential to collect tumor and blood samples before and after treatment provides a unique opportunity to study the immune response induced by CPMV nanoparticles and identify immune cells and molecular events associated with the response. These biomarkers could be used to monitor response to this therapy in humans in future studies.”

Future studies include expanding this new approach to a larger number of IMC dog patients, with the ultimate goal of implementing CPMV immunotherapy as a new treatment for human patients with IBC and other solid tumors. These results with in situ vaccination treatment with CPMV immunotherapy portends a groundbreaking therapy for both IMC and IBC patients who lack specific therapies.

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

Hugo Arias-Pulido, PhD, is the senior scientist in the Steven Fiering lab, and lead author of the study. His research interests include developing optimal animal models to evaluate efficacy of novel agents, including immunotherapeutic compounds.

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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 51 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.

About the Geisel School of Medicine

Founded in 1797, the Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, healthcare policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of America’s leading medical schools, Dartmouth’s Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in healthcare.

About Dartmouth-Hitchcock Health

Dartmouth-Hitchcock Health is a national leader in health care. We are New Hampshire’s only academic health system and the state’s largest private employer, serving a population of 1.9 million across northern New England. Dartmouth-Hitchcock Health and our nearly 2,000 providers are all deeply committed to serving the healthcare needs of our communities and to providing each of our patients with exceptional, personal care. Dartmouth-Hitchcock Medical Center is consistently named the #1 hospital in New Hampshire by U.S. News & World Report. Dartmouth-Hitchcock Health includes the Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation; the Children’s Hospital at Dartmouth-Hitchcock (CHaD), the state’s only children’s hospital; and member hospitals and clinics across the state. Dartmouth-Hitchcock Health performs cutting-edge research and clinical trials in partnership with the Geisel School of Medicine at Dartmouth, and trains nearly 400 medical residents and fellows annually.